Objective: The presence of previously unrecognised cells has been detected during ultrastructural investigations of normal and atherosclerotic human aortic intima. These cells show many of the morphological features of dendritic cells. Because dendritic cells can be stained positively for S-100, the aim of this study was to determine whether S-100 immunoreactive cells can be detected in the arterial wall, and if so, how they are distributed in normal intima and in atherosclerotic lesions. Methods: Paraffin sections of human aorta and carotid artery were stained with S-100 antibody, using an immunoperoxidase technique. Results: In areas of the arterial wall without histological signs of atherosclerosis, S-100 positive cells were found but they were relatively few compared with the much greater numbers of S-100 positive cells showing dendritic cell morphology in atherosclerotic lesions. Different atherosclerotic lesions were found to contain different numbers of S-100 positive cells. In fatty steaks and in uncomplicated atheromatous plaques, many S-100 positive cells were present, but in complicated atherosclerotic lesions fewer such cells were found. Conclusions: Although the nature of these S-100 positive dendritic cells needs further clarification, the results suggest that these cells play an important role in the development of atherosclerotic lesions, and may represent antigen presenting dendritic cells in human arteries. If the S-100 positive cells prove to be part of the family of antigen presenting dendritic cells, the findings have important implications for understanding atherogenesis and offer a link between immune mechanisms and atherosclerotic lesion formation.