Ubiquitous viruses such as members of the human herpes virus group, particularly cytomegalovirus (CMV), have been proposed to be clinically important agents in the initiation and progression of atherosclerosis. Antibodies to CMV and herpes simplex virus type 1 (HSV1) and type 2 (HSV2) were determined in 340 matched case-control pairs from the Atherosclerosis Risk in Communities (ARIC) Study. Cases were defined by B-mode ultrasonography as persons with thickened carotid artery walls consistent with early atherosclerosis but without a history of cardiovascular disease. Controls were defined as persons without thickened walls or history of cardiovascular disease. The case-control odds ratio for CMV antibodies was 1.55 (P = .03), for HSV 1.41 (P = .07), and for HSV2 0.91 (P = .63). When adjustment was made for potential confounders, the odds ratios were 1.36 for CMV (P = .24), 1.21 for HSV1 (P = .45), and 0.61 (P = .05) for HSV2. These results suggest a modest association between CMV and asymptomatic carotid wall thickening consistent with early atherosclerosis.