As the acute infectious diseases recede in importance, and as the number of people surviving into middle and old age increases, the chronic 'degenerative' diseases assume greater importance as causes of death and disability. Of these diseases, atherosclerosis is by far the most prevalent and its consequences the most devastating. The search for the cause of atherosclerosis is consuming large amounts of resources of both money and research talent. As yet, the cause remains unknown. Much of the research effort into atherosclerosis has been concerned with lipid metabolism. This is based on the knowledge that abnormalities of certain lipids and lipoproteins predispose to cardiovascular disease. Often the research has not been directly related to atherosclerosis and it is only recently that widespread attention has been paid to the artery. The development of methods of growing vascular endothelial and smooth muscle cells in culture has made possible detailed studies of the biology of the arterial wall. There are a number of reasons why investigations of lipid metabolism alone will not identify the cause of atherosclerosis. First, only a minority of patients with cardiovascular disease have abnormal circulating lipids and lipoproteins. Second, there are three major predisposing factors for atherosclerosis which cannot be entirely explained by abnormal lipid metabolism - age, sex, and diabetes mellitus. Third, it is now clear that lipid is only one component of the atheromatous plaque, and incorporation of lipid may be a late feature of the development of the lesion.