During progression of atherosclerosis the overlying endothelial cells alter their expression of some surface molecules. Circulating levels of such molecules may be quantified. We investigated the effect of omega-3 fatty acids (n-3 FA) on the levels of tissue plasminogen activator antigen, von Willebrand factor, and the soluble forms of thrombomodulin, P-selectin, E-selectin, and vascular cell adhesion molecule-1 in 54 patients with coronary heart disease. Twenty-three of the patients had taken 5.1 g/d n-3 FA for 6 months (group I) and 31 were given corn oil as placebo (group II). For another 4 weeks ("the study period") they all got 5.1 g/d of n-3 FA. Compliance was confirmed by demonstration of changes in relevant fatty acids in serum phospholipids. At baseline, significant differences between the groups were found with lower median values of von Willebrand factor (128% versus 147%) and soluble thrombomodulin (24.9 versus 32.5 ng/mL) and higher median values of soluble E-selectin (41.4 versus 35.5 ng/mL) and soluble vascular cell adhesion molecule-1 (573 versus 473 ng/mL) in group I. During the study period differences in changes between the groups were found; tissue plasminogen activator antigen and soluble thrombomodulin decreased (P for difference between the groups 0.001 and 0.015, respectively), whereas soluble E-selectin and soluble vascular cell adhesion molecule-1 increased (P for difference between the groups <0.01 for both) in group II relative to group I. Our results indicate that n-3 FA supplementation decreases hemostatic markers of atherosclerosis, whereas markers of inflammation may be increased. The latter may be the result of lipid peroxidation as a simultaneous decrease of vitamin E and increase in thiobarbituric acid-reactive substances were observed.