Expression of thrombomodulin (TM) in atherosclerotic lesions of the human aorta (8 cases of diffuse intimal thickening, 4 fatty streaks, 11 atheromatous plaques, and 5 fibrous plaques) as well as in undiseased aortas of 5 infants obtained at autopsy was studied immunohistochemically using a novel polyclonal antibody against human TM. TM was expressed in intimal smooth muscle cells (SMC) besides endothelial cells and foamy macrophages in almost all patients (26/28). In addition, medial SMC in adult cases over 27 years of age expressed TM. In young adults with diffuse intimal thickening under 26 years of age, medial SMC showed no TM expression whereas intimal SMC did show it. Both intimal and medial SMC in infants showed no TM expression. An immunofluorescence method showed TM expression in cultured adult human SMC. These findings indicate that TM expression in SMC may depend on patient age as well as lesion type of atherosclerosis.