Background/Purpose: Atherosclerosis plays an important role in stroke. A microbiological infection has been suggested to be involved in the pathogenesis of atherosclerosis, in particular the human cytomegalovirus (HCMV). The objective of this study was to determine the association between HCMV infection and atherosclerosis of the internal carotid arteries in patients of Chinese Han ethnicity with ischemic stroke. Methods: HCMV DNA and antigen were detected in atherosclerotic internal carotid arteries from 35 patients with ischemic stroke and 20 controls from a Chinese Han ethnic population. Immunohistochemistry, in situ hybridization and polymerase chain reaction were used to detect the HCMV immediate early (IE) and late (L) antigen as well as DNA in the vascular walls. Results: We observed that the proportion of cases that tested positive for HCMV IE but not L antigen and DNA was statistically greater in stroke patients compared with the control population. Conclusion: HCMV IE antigen and DNA were associated with the pathological process of atherosclerosis. The vessel wall might be the infection site of the dormant virus. [J Formos Med Assoc 2008;107(10): 774-781]