The biological properties of cytomegalovirus (CMV) are consistent with a potential role in the pathogenesis of atherosclerosis. The evidence of such a role has so far been circumstantial, but CMV nucleic acid is beginning to be reported with increasing frequency in the arterial wall. Arterial specimens from 135 patients who underwent vascular surgery for symptomatic atherosclerotic vessel disease were analyzed by PCR for the presence of CMV nucleic acid. Samples were studied from the atheromatous plaque area and from uninvolved aortic tissues of patients undergoing surgery for vascular disease. One primer pair (LA) was used for detection of a late gene, and two other primer pairs (E1 and E2) were used for the immediate early gene region. Serum antibody to CMV was measured by radioimmunoassay. With the late gene primer, CMV nucleic acid was found in 76% of the tissue specimens tested, whereas the E2 gene primer complementary to the transforming mtr2 region was reactive in 90% of the arterial samples. There was no significant difference in the prevalence of CMV DNA in atherosclerotic plaque tissue and in uninvolved aortic tissue from the patients. A second early gene primer was not reactive with the tissue specimens, although it gave positive results with the positive control of infectious virus. Serum antibody to CMV was detected in 86% of the patients in whose tissue CMV DNA was demonstrated. CMV DNA was detected in a high proportion of atherosclerotic plaque tissues as well as in uninvolved aortic tissue of surgical patients, suggesting that latent CMV infection of the arterial wall may be a common occurrence in patients with atherosclerosis.