Discovery of the mechanism for V(D)J hypermutation remains a basic goal of immunology despite the best efforts of many labo ratories. The existence of catalyzed, site-specific mutation and its exploitation for the somatic evolution of lymphocytes are re markable adaptations, yet since the discovery of hypermutation in 1970 (see cover), much hard work has generated little. Indeed, our knowledge of what is probably absolutely required for the mutator's action can be succinctly expressed: /g gene enhancers. Table 1 of Winter et a .'s chapter puts into a historical perspec tive how our notions of the mutator have changed over the years. Despite these modest gains, most of us feel that this is the best of times. Our work has not only shown us what the mutator is not, it has also, like an artist's preliminary sketch, defined the questions and experiments we must face without diminishing the potential for new biology. In short, it is great fun to toil against a significant and enigmatic problem."

This book includes articles relating to presentations given in a variety of forms (lectures, posters, contributions to round tables, software presentations) at the 5th International Biothermokinetics Meeting held in Bordeaux-Bombannes, September 23-26, 1992. The fact that not just lectures were considered for these proceedings reflects the aims of BTK meetings to instigate discussion, promote scientific cooperation and confront as many different ideas as possible with each other (at best heretical ones). BTK conferences have expanded more and more; 130 participants came to the 1992 meeting from 20 countries. It was therefore necessary to hold the round tables in parallel sessions. It is difficult to have an unbiased feeling of what should be selected as the salient features of the meeting. As the name suggests, Biothermokinetics embraces thermodynamic and kinetic approaches to experimental and theoretical investigations of biological processes, in particular at the cellular level. This "classical" point of view is mainly represented in the chapter "Thermodynamics and Kinetics of Transport Processes and Biological Energy Transduction."

Understanding how the brain works is undoubtedly the greatest challenge for human intelligence and one of the most ambitious goals of contemporary science. We are certainly far from this goal, but significant advancements in several fields of Neuroscience and Neurobiology are being obtained at an increasing pace. The NATO ASI School in Neurobiology, held in Erice May 2-12,1995, as the 23rd Course of the International School of Biophysics, provided an update on three basic topics: Biophysics and Molecular Biology ofIon Channels, Sensory Transduction, and Higher Order Functions. Current knowledge on these subjects was covered by formal lectures and critical discussions between lecturers and participants. This book collects original contributions from those scientists who attended the School. Many students presented their results in poster sessions, steering lively informal discussions. A selection of these contributions is also included. A major portion of the program of the School was devoted to a general overview of current trends of thought and experimental approaches in neurobiology, emphasising the importance of understanding molecular aspects of the elementary events underlying sensory transduction and processing in the nervous system, without indulging however in a pure reductionistic view of such complex phenomena. Recent studies of molecular biology and the electrophysiology of heterologously expressed ionic channels, have shed new light on the molecular mechanisms underlying ionic permeation of excitable membranes and its regulation by physical and chemical parameters.

The Association Internationale de Recherche sur la Circulation Osseuse, A.R.C.O., was founded in London in December 1989 by a small group of doctors, surgeons and researchers in basic sciences who had been involved for many years in the study of bone circulation and its disorders. They had met several times in Toulouse, during the International Symposia on Bone Circulation held there since 1973 and they wished to carry their contacts further. In founding A.R.C.O., they established as their primary aims the encouragement and furtherance of research, organisation of meetings and promotion of knowledge on the subject. At the present time, the Association has over a hundred members from more than bone tissue twenty countries in Europe, America and Asia. All have the conviction that and its pathology can only be truly known and studied if one has an understanding of its vascular system and the way its circulation functions. This concept, apparently beyond question, has not yet been adopted by all physicians and scientists who are interested in bone. From time to time, one comes across teaching programmes on bone patho logy which make no mention of bone circulation.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

Similarities in structure and function between pigs and human beings include size, feeding patterns, digestive physiology, dietary habits, kidney structure and function, pulmo nary vascular bed structure, coronary artery distribution, propensity to obesity, respiratory rates, tidal volumes and social behaviors. Since the pig is an omnivore, it provides an adaptable model to evaluate chronic and acute exposures to xenobiotics such as alcohoL caffeine, tobacco, food additives and environmental pollutants. Swine have been used successfully as models to evaluate alcoholism, diabetes, absorption, digestion, total paren teral nutrition, organ transplantation, atherosclerosis, exercise, hypertension. hemorrhagic hypotension, melanoma, gingivitis, obstructive and reflux nephropathy. osteochondrosis. dermal healing and septic shock. A severe and worsening shortage of organs and tissues for transplantation in patients with severe organ failure has encouraged the consideration of inter species or xenotransplan tation. In developing programs toward this end, the pig generally is viewed as the preferred donor because of its size, physiology and availability. The pig harbors relatively few diseases which could be transmitted inadvertently to human patients. The ability to genetically modify swine to ameliorate the consequences of the human immune response offers a further significant advantage. Another important consideration for an animal model is that basic biologic back ground information be available for investigators to design future prospective studies."

Since its inception in 1973, The International Society on Oxygen Transport to Tissue (ISOTT) has provided a unique forum to facilitate and encourage scientific interaction and debate. Welcoming scientists and clinicians from a broad spectrum of disciplines, each with their own particular skills and expertise, ISOTT unites them under the common theme of oxygen transport. The successful blend of scientific presentations and informal discussion which characterizes ISOTT is epitomized best by the many fundamental discoveries and technical advancements which it has spawned. The breadth and strengths of The Society's scientific base promotes the rapid progression of ideas from theoretical concepts to rigorous scientific testing and often, ultimately to the clinical arena. Each publication of the ISOTT proceedings has been recognized by Science Citation Index listing and the papers frequently establish scientific precedents and become considered as standard works in their respective fields. The 21st ISOTT Meeting was held in San Diego from August 14th through August 18th, 1993. The San Diego Meeting attracted about 150 registrants and 40 accompanying persons. Ten state-of-the-art lectures were presented by international experts in ~ transport and there were in addition two symposia -one dealing with assessment of tissue hypoxia and the other with functional heterogeneity in different organ systems. There were 100 free communications, consisting of posters accompanied by an abbreviated oral summary. All manuscripts were reviewed by the Editors for form and content, but as is customary for the ISOTT proceedings, rigorous scientific peer review was not undertaken.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

The research field of somatosensory processing in mammals has experienced revolutionary changes in recent years. Accumulation of basic and clinical data has greatly accelerated, and new phenomena have emerged. With the aid of new, refined methods, molecular and cellular changes have been described, underlying the signal transduction-transmission between the internal/external environment and the central nervous system have been described. The discovery of the interaction between the nervous and the immune system has, for example changed our view on the development of inflammatory diseases, while the cloning of genes encoding different trophic factors has boosted studies revealing profound changes in the regeneration of neurons, and induction of changes in phenotype. The study of the pre-and postsynaptic modulation of transmitter release, and the examination of the combined effects of amino acid and peptide transmitters has become recently possible by using cultured cell lines and in vitro techniques. Although it is in embryonic state, computational properties of single DRG cells under normal and pathological conditions are being investigated. Results soon or later will have a great impact on pain research and consequently ultimately in clinical pain management. This brief introduction indicates how our knowledge of the somatosensory system has increased dramatically recently. However, many investigators cultivate only a very specific field in the growing area of somatosensory research and find it difficult to integrate a more universal knowledge of their work.

I have spent less time in the arid zone in the last few years than I did during the 1960's, 1970's and early 1980's. This results from a progression through age and a career structure which gradually shifted the emphasis of my work from being essentially field-oriented to essentially office-hound. When, therefore, I was asked by John Cloudsley-Thompson to undertake the writing of this hook I hesitated for two reasons. One reason was that, although I now had access to good library facilities and kept up with the literature on the arid zones and their fauna, I was not sure that a sedentary and pleasant life in a temperate highland island in tropieal Africa would provide a mental attitude suitable to writing a hook which related to areas where life is usually nomadie and often extremely disagreeable. The other reason was that I was uncertain whether I could devote the time necessary to researehing and writing the hook on top of my professional (which now specifical ly excluded research in the arid zones and on camels) and social (new-found and time-consuming) commitments. In the event I accepted and the fates were kind to me. By some peculiar combination of circumstances I was given the opportunity to spend a considerable part of the first half of 1988 in some of the driest areas of the globe. I had already visited all of the locations used for the construction of Fig. 2."

It has been great fun to write this book, even though it has taken longer than planned, and occasionally been exasperating. The most difficult problem was deciding what to exclude among so many interesting things, because the available material usually exceeded the space. Because a book like this covers so many aspects, each component must be limited. This book is intended for graduate and undergraduate students as well as professional scientists who want to work with animal flight or to gain some insight into flight mechanics, aerodynamics, energetics, physiology, morpho logy, ecology and evolution. My aim has not been to give the whole mathe matical explanation of flight, but to provide an outline and summary of the main theories for the understanding of how aerofoils respond to an airflow. I also hope to give the reader some insight into how flight morphology and the various wing shapes have evolved and are adapted to different ecological niches and habitats."

During the past decade there has been a dramatic expansion of our knowledge on phospholipases in general, and phospholipase A2 (PLA2) in particular. Progress in this field has been evident on many fronts, with novel information rapidly accumulating in the literature regarding the chemistry and molecular biology of this enzyme and its role in many important physiological processes. These include cellular signal transduction via the G-protein cycle, and in the generation of many cellular mediators, such as the platelet activating factor (PAF) and the eicosanoids that participate in the initiation and propagation of inflammation, to mention a few. This symposium was organized to obtain an overview of current investigations on this enzyme from the standpoint of its chemistry, molecular biology and physiology. Another important focus of this symposium concerns the regulation of PLA2, including endogenous and synthetic inhibitors and activators of this enzyme. To review these important areas in PLA2 research we invited scientists who made significant contributions in this field. The papers in this volume are organized to emphasize the recent advances in several areas of investigation, including: (I) the structure and mechanism of action of PLA2, (2) mechanism of activation of PLA2, (3) molecular biology, physiology and endogenous inhibitors of this enzyme and finally, (4) clinical investigations emphasizing the pathophysiological role of this enzyme in human diseases. The first article in this volume is by Dr.

The Springer Handbook of Auditory Research presents a series of compre hensive and synthetic reviews of the fundamental topics in modern auditory research. The volumes are aimed at all individuals with interests in hearing research, including advanced graduate students, postdoctoral researchers, and clinical investigators. The volumes are intended to introduce new in vestigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume is intended to present a particular topic comprehensively, and each chapter serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in peer-reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation, rather than on those for which a literature is only beginning to develop. New research areas will be covered on a timely basis in the series as they begin to mature."

Many organisms have evolved the ability to enter into and revive from a dormant state. They can survive for long periods in this state (often even months to years), yet can become responsive again within minutes or hours. This is often, but not necessarily, associated with desiccation. Preserving one's body and reviving it in future generations is a dream of mankind. To date, however, we have failed to learn how cells, tissues or entire organisms can be made dormant or be effectively revived at ambient temperatures. In this book studies on organisms, ranging from aquatic cyanobacteria that produce akinetes to hibernating mammals, are presented, and reveal common but also divergent physiological and molecular pathways for surviving in a dormant form or for tolerating harsh environments. Attempting to learn the functions associated with dormancy and how they are regulated is one of the great future challenges. Its relevance to the preservation of cells and tissues is one of the key concerns of this book.

The field of olfactory research and chemical communication is in the early stages of revolutionary change, and many aspects of this revolution are reflected in the chapters in this book. Thus, it should serve admirably as an up-to-date reference. First, a wide range of vertebrate groups and species are represented. Second, there are excellent reviews of specific topics and theoretical approaches to communication by odors, including chapters on signal specialization and evolution in mammals, the evolution of hormonal pheromones in fish, alarm pheromones in fish, chemical repellents, the chemical signals involved in endocrine responses in mice, and the controversy over human pheromones. Third, there are exciting new findings presented in numerous specific topic areas, such as the chemis try of pheromones in a wide range of species (salamanders to elephants), the chemistry of proteins that control the release of pheromones, the molecular biology and physiology of detection, coding and response to odor signals, the effects of experience on sensitivity to odors, the role of genes of the immune system in odor production and in human mate choice, the function and perception of scent over-marks, the recognition of individuals and kin by odors, the influence of odors on predator-prey interactions, and the use of odors to help control pests. This book is an offshoot of the Eighth International Symposium on Chemical Sig nals in Vertebrates, held at Cornell University in Ithaca, New York, July 20-25, 1997, hosted and organized by Bob Johnston.

Space missions subject human beings or any other target of a spacecraft to a radiation environment of an intensity and composition not available on earth. Whereas for missions in low earth orbit (LEO), such as those using the Space Shuttle or Space Station scenario, radiation exposure guidelines have been developed and have been adopted by spacefaring agencies, for exploratory class missions that will take the space travellers outside the protective confines of the geomagnetic field sufficient guidelines for radiation protection are still outstanding. For a piloted Mars mission, the whole concept of radiation protection needs to be reconsidered. Since there is an increasing interest ci many nations and space agencies in establishing a lunar base and lor exploring Mars by manned missions, it is both, timely and important to develop appropriate risk estimates and radiation protection guidelines which will have an influence on the design and structure of space vehicles and habitation areas of the extraterrestrial settlements. This book is the result of a multidisciplinary effort to assess the state of art in our knowledge on the radiation situation during deep space missions and on the impact of this complex radiation environment on the space traveller. ]t comprises the lectures by the faculty members as well as short contributions by the students given at the NATO Advanced Study Institute "Biological Effects and Physics of Solar and Galactic Cosmic Radiation" held in Armacao de Pera, Portugal, 12-23 October, 1991.

A number of remarkable recent breakthroughs have made the study of nitric oxide one of the most exciting fields in physiology and pathophysiology. This authoritative edited volume reviews the progress to date and opens perspectives to novel diagnostic and therapeutic strategies. The contributors are leading authorites, in most cases the investigators who have pioneered the ideas explored in the book.

In the past few years there has been the increased recognition that the effects of oxidative stress are not limited to the damage of cellular constituents. There is now evidence that reactive oxygen species (ROS) can alter cell function by acting upon the intermediates, or second messengers, in signal transductions. Such effects on signaling mechanisms probably account for the role of oxidative stress in inflammation, aging, and cancer. This volume brings together internationally recognized researchers in both the major areas covered by the book, oxidative stress and signal transduction. The work is organized in three sections. The first deals with the immediate cellular responses to oxidative stress and the production of second messengers. The second details the connection between second messengers and the gene. The third part looks more closely at the level of the gene.

Presented with a choice of evils, most would prefer to be blinded rather than to be unable to move, immobilized in the late stages of Parkinson's disease. Yet in everyday life, as in Neuroscience, vision holds the centre of the stage. The conscious psyche watches a private TV show all day long, while the motor system is left to get on with it "out of sight and out of mind. " Motor skills are worshipped at all levels of society, whether in golf, tennis, soccer, athletics or in musical performance; meanwhile the subconscious machinery is ignored. But scientifically there is steady advance on a wide front, as we are reminded here, from the reversal of the reflexes of the stick insects to the site of motor learning in the human cerebral cortex. As in the rest of Physiology, evolution has preserved that which has already worked well; thus general principles can often be best discerned in lower animals. No one scientist can be personally involved at all levels of analysis, but especially for the motor system a narrow view is doomed from the outset. Interaction is all; the spinal cord has surrendered its autonomy to the brain, but the brain can only control the limbs by talking to the spinal cord in a language that it can understand, determined by its pre-existing circuitry; and both receive a continuous stream of feedback from the periphery.

The past two decades have witnessed an unprecedented growth in the field ofneuroendocrinology. The conjoint research contributions by clinicians and basic scientists have promulgated revolutionary concepts at a breakneck speed. This first volume in Clinical Surveys in Endocrinology, The Pituitary Gland, has been written with but one purpose in mind: to integrate the current knowledge in this dynamic field with the existing body of information already available to the clinician. The chapters in this book attempt to portray current research information seen through the eyes of a clinician. The contributions of pioneers in each field have been placed in a perspective relevant to the practicing endocrinologist. The selection of the almost 1500 references from a bewil of literature has been inftuenced by the degree to which these dering body articles-original as weil as review papers-contributed to the growth of pi tuitary endocrinology. Despite the most scrutinizing attempts, it is inevitable and regrettable that works of importance must be excluded due to the practical limitations of any comprehensive work. Nevertheless, to the researcher these references are complete enough to serve as a significant resource. To the reader who wishes to gain an indepth clinical perspective of pituitary disor ders, this work is written precisely from that vantage point. The single authorship of this work notwithstanding, several friends have been instrumental in the completion of this work. I deeply appreciate the incessant zeal and excellent assistance of Ms."

I had the good fortune to first meet Gerald Kuchling in 1985 when attending a conference held at the CNRS research centre, the Centre d'Etudes Biologiques des Animaux Sauvages (CEBAS), which is a wonderful scientific field station tucked away in the Foret de Chize, not far from the southwest town of Niort in France. The topic of the meeting, which included many invited overseas scientists, was "Physiological Regulations as Adaptive Mechanisms", and it was superbly organised by Ivan Assenmacher and Jean Boissin who together edited the impor- tant volume of papers published from the meeting. My stay in Chize was, unfor- tunately, cut short as the wife of a very close colleague died on the night of the first day of the meeting and I had to return to Paris to assist with the funeral -but not before I had the chance to meet and talk with Gerald. He was presenting some of his work on a terrestrial tortoise (or turtle depending upon one's origins) - Testudo hermanni - a species that is now extremely rare in France but still relatively abundant in the then Yugoslavia. Gerald had been working in Yugoslavia, collecting blood samples from both males and females in an attempt to decipher details of its reproductive biology.

This book is a compendium of proceedings from the Symposium on Growth Hormone II: Basic and Clinical Aspects. The intent of the sym posium was to review current aspects of the rapidly expanding science of growth hormone (GH) neuroendocrinology, especially those develop ments that occurred since our last meeting in 1985. The meeting was timely since there have been many new and exciting developments in basic research on the GH axis, and several new clinical applications for GH other than growth have been identified. For example, significant strides have been made into use of the bioengineered hormone as an anabolic in debilitated states and as an immunorestorative agent. Both these areas have received most attention as they relate to geriatric popu lations. Furthermore, recent focus on a novel family of GH secretagogues that complement the action of GHRH has shown that in animal models, these compounds have the potential to restore GH secretion in deficient or insufficient states, including growth retardation, obesity, and aging. Accordingly, these xenobiotics may have significant potential as drug products to stimulate physiological GH secretion and, thus, resist or reverse some of the maladaptive changes in form and function resulting from GH insufficiency. The importance of these agents as drug candidates is underscored by the diversity of molecules that have been studied by various pharmaceutical companies and the recent discovery that non peptide analogs with high oral bioavailability can be synthesized."

The auditory system has a remarkable ability to adjust to an ever-changing environment. The six review chapters that comprise Plasticity of the Central Auditory System cover a spectrum of issues concerning this ability to adapt, defined by the widely applicable term "plasticity." With chapters focusing on the development of the cochlear nucleus, the mammalian superior olivary complex, plasticity in binaural hearing, plasticity in the auditory cortex, neural plasticity in bird songs, and plasticity in the insect auditory system, this volume represents much of the most current research in this field. The volume is thorough enough to stand alone, but is closely related a previous SHAR volume, Development of the Auditory System (Volume 9) by Rubel, Popper, and Fay. The book fully addresses the difficulties, challenges, and complexities of this topic as it applies to the auditory development of a wide variety of species.

Reproductive wastage is a major inefficiency in all livestock production with embryonic mortality accounting for a major portion of this loss. Accordingly the Commission of the European Communities encouraged the organisation of a seminar on embryonic mortality in farm animals which was held in Brussels on the 11th and 12th of December 1984. This book contains the text of the papers, discussions and final summary presented at that Seminar. As a background to the Seminar, the extent and timing of embryonic loss was described for farm animals. Particular consideration was then given to the various mechanisms and signals, both embryonic and uterine in origin, that are so far known to be involved in the establishment of pregnancy. Possible causes of embryonic death including physiological, endocrinological, genetic and immunological components were outlined and discussed. The final summary contains general conclusions from the Seminar and recommendations for future research work on this topic. J.M. Sreenan M.G. Diskin July 1985. ******************** THE EXTENT AND TIMING OF EMBRYONIC MORTALITY IN THE COW J. M. Sreenan & M. G. Diskin, The Agricultural Institute, Belclare, Tuam, Galway, Ireland ABSTRACT The extent and timing of embryonic mortality in heifers, normal cows and repeat breeder cows has been reviewed.

This volume, The Adrenal Gland, is the second in the Clinical Surveys in Endo crinology series. Like its predecessor on the pituitary gland, this work is written with one purpose in mind-to view the vast, relevant adrenal literature through a clinician's eyes. The intricate, and often complex, interrelationship between the clinical and research perspectives of "adrenology" poses a challenge. This is, in part, due to the commonly held belief that the milieux of steroid hormone research and clinical medicine are parallel phenomena, not destined to meet. But the twain do meet, and often with relative ease, when viewed as twin facets of the same gem. The view presented in this work is from the vantage point of the clinical endocrinologist who applies the research literature to understand adre nal diseases more clearly. Adrenal pathology is arguably the most fascinating of all endocrinopathies. The images of patients suffering from adrenal diseases are of kaleidoscopic quality: the newborn child with ambiguous genitalia, in whom the very first ritual of assigning sex becomes shrouded with uncertainty; the revitalized pa tient with hitherto undiagnosed Addison's disease, who but for the cognitive powers of the endocrinologist would have ultimately succumbed, undiagnosed; the virilized female with adrenal tumor and its attendant onslaught on the body and mind; the febrile patient with pheochromocytoma masquerading as fever of undetermined origin for months."