An avian herpesvirus is known to cause atherosclerosis in chickens. The same virus can induce a proliferative disease, malignant lymphoma, suggesting that this agent may also have transforming potential and thus stimulate the proliferation of arterial smooth muscle cells, a prominent feature of atherogenesis. The evidence for involvement of cytomegalovirus (CMV), a member of the human herpesvirus family, in atherosclerosis is much more circumstantial. The finding of CMV antigen and nucleic acid sequences in arterial smooth muscle cells of humans suggests that viral infection of the arterial wall may be common in the general population, including patients with severe atherosclerosis. In seroepidemiological studies, high levels of CMV antibodies were found to be associated with clinically manifest atherosclerotic disease, suggesting that a periodically activated latent infection or a continuously active infection is present in patients with atherosclerosis. Since the viral genome but not infectious virus is found in arterial cells, the artery itself may be the site of CMV latency. Of particular significance is the recent finding that heart transplant recipients, who are immunosuppressed, and who are also actively infected with CMV, are prone to develop accelerated atherosclerosis in the transplanted organ. Although suggestive, these observations by themselves do not demonstrate that viruses have a role in the pathogenesis of atherosclerosis, but they support a working hypothesis of the steps involved.