OBJECTIVE In the carotid bifurcation, atherosclerotic plaques usually develop in the outer wall of the internal carotid artery. The aim of this study was to analyze the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the carotid bifurcation. These molecules play a role in inflammatory cell recruitment and atherosclerosis. METHODS We examined the expression of ICAM-1, VCAM-1, and E-selectin in 22 human carotid bifurcation specimens by means of immunohistochemistry. Double immunostaining was performed with antibodies against CD-3, CD-31, CD-68, and alpha-smooth muscle actin combined with each of the cell adhesion molecule antibodies. In situ hybridization for ICAM-1 was performed in selected specimens. RESULTS A profound focal expression of ICAM-1 in the outer wall of the internal carotid artery could be demonstrated (86% of all specimens). This focal expression could be shown in histologically normal appearing bifurcations of young adults. ICAM-1 was expressed by subsets of macrophages and smooth muscle cells and by endothelial cells. VCAM-1 and E-selectin showed no focal expression and were not found in normal carotids. In advanced plaques all three adhesion molecules-ICAM-1, VCAM-1, and E-selectin-were expressed. CONCLUSIONS We were able to demonstrate a focal expression of ICAM-1 in the outer lateral wall of the internal carotid artery, which is a high-risk region for the development of atherosclerotic lesions.