Foot-and-mouth disease (FMD) has been recognized in printed records dating from the sixteenth century, and since the eradication of rinderpest (cattle plague) in the early part of the twentieth century it has been rec- nized as the most important and feared disease of cattle and other dom- tic livestock. The beginning of the twenty-first century brought the worst outbreak of FMD ever experienced in England, which had been completely free of the disease for 33 years. This tragic epidemic, which spread to Northern Ireland, Scotland, France and the Netherlands with severe e- nomic consequences, emphasized the need for further research into better methods for the detection and control of the disease. FMD is caused by a small RNA virus which is highly contagious and can survive in meat and other animal products for long periods at normal pH levels. The virus typically infects cloven-hoofed animals, including c- tle, goats, pigs and sheep, as well as a wide range of non-domesticated a- mals in regions of the world where FMD virus is endemic, such as the Af- can continent. There are seven recognized serotypes of FMD virus, with numerous subtypes, and as a consequence vaccine production and administration is complex and a major debate surrounds every disease outbreak regarding the relative merits of vaccination as opposed to the slaughter of all infected animals.

2 D. Immunological Response . . . . . . . . . . . . . . . . . . . . 78 1. Thymectomy in LDV Infection . . . . . . . . . . . . . . . . 81 2. Effect of LDV Infection on Immune Response to Various Antigenic Stimuli. . . . . 82 E. Tumour Growth . . 87 F. Histological Changes 91 VII. Ecology . . . . . . . 97 VIII. Laboratory Methods. . 100 A. Blood Samples from Mice for LDH Estimation . 100 B. Estimation of Plasma LDH Activity . . 101 1. Quantitative Methods. . . . . . . . 101 a) Determination of Plasma LDH by Spectrophotometric Method (Backward Reaction) . . . . . . . . . . . . . . . 101 b) Determination of Plasma LDH by Spectrophotometric Method (Forward Reaction) . . . . . . . . . . . . . . . . 102 c) Determination of Plasma LDH by Colorimetric Method 103 2. Qualitative Method. . . . . . . 103 3. Units of LDH Activity . . . . . 104 C. Diagnosis of LDV Infection in Miee. 105 D. Virus Titration. 105 References. . . . . . . . . . . . . . . . 106 We wish to express our thanks to our many colleagues who generously provided us with preprints of their work, and unpublished observations. We are particularly indebted to those who donated prints of their electron micrographs of the virus. I. Introduction Inapparent virus infections of experimental animals and tissue culture systems present to the investigator a problem which it is impossible to overcome completely. Although all recognised viruses can be excluded from an experimental system, previously unsuspected viruses causing no obvious effects ('silent' viruses) will continue to be discovered. A truly silent virus would replicate, causing no change in its host cell, damage to infected tissue or immune response and would pre sumably be of no consequence."

Foot-and-mouth disease (FMD) has been recognized in printed records dating from the sixteenth century, and since the eradication of rinderpest (cattle plague) in the early part of the twentieth century it has been rec- nized as the most important and feared disease of cattle and other dom- tic livestock. The beginning of the twenty-first century brought the worst outbreak of FMD ever experienced in England, which had been completely free of the disease for 33 years. This tragic epidemic, which spread to Northern Ireland, Scotland, France and the Netherlands with severe e- nomic consequences, emphasized the need for further research into better methods for the detection and control of the disease. FMD is caused by a small RNA virus which is highly contagious and can survive in meat and other animal products for long periods at normal pH levels. The virus typically infects cloven-hoofed animals, including c- tle, goats, pigs and sheep, as well as a wide range of non-domesticated a- mals in regions of the world where FMD virus is endemic, such as the Af- can continent. There are seven recognized serotypes of FMD virus, with numerous subtypes, and as a consequence vaccine production and administration is complex and a major debate surrounds every disease outbreak regarding the relative merits of vaccination as opposed to the slaughter of all infected animals.