The investigations reviewed in this paper provide evidence that a member of the herpesvirus family can cause atherosclerosis in chickens. In vitro experiments, as well as studies of arteries from infected birds, suggest that a virus-induced alteration of cellular metabolism, which results in the accumulation of cholesterol and cholesteryl esters, may be the primary mechanism in development of viral atherosclerosis. In addition, the fact that the same avian virus induces a malignant lymphoma suggests that it may also have the potential to stimulate the proliferation of other cells, notably arterial smooth muscle cells. The evidence for involvement of one or more members of the herpesvirus family in human atherosclerosis is much more circumstantial. Cytomegalovirus (CMV) is prevalent, increasing with age, so that a majority of the human population becomes infected by adulthood. As with other herpesviruses, the infection with CMV is usually subclinical or latent. Although the sites of latency for CMV have not been established, both smooth muscle and leukocytes are likely possibilities. The observations of viral antigens and nucleic sequences, but not infectious virus, in arterial smooth muscle cells suggests that latent CMV infection of the arterial wall may be common in patients with atherosclerosis.