Activity of plasminogen activator inhibitor-1 (PAI-1) in human blood correlates with thrombotic tendency and with serum triglyceride concentrations. Since intake of fish-derived omega-3 polyunsaturated fatty acids (PUFA) decreases serum triglycerides, we examined the effects of omega-3 PUFA maximum eicosapentaenoic acid (Max EPA) intake on PAI-1 levels in eight patients with coronary artery disease and in four normal subjects. After 4 weeks of Max-EPA intake by coronary artery disease patients, serum triglyceride concentrations and PAI-1 levels decreased 43 +/- 8% and 21 +/- 5%, respectively (both p less than or equal to 0.01) without any change in tissue plasminogen activator (TPA) levels. No changes were noted at 1 week of Max EPA intake in normal subjects, but at 3 weeks serum triglyceride concentrations and PAI-1 levels decreased 32 +/- 13% and 22 +/- 4%, respectively (p less than or equal to 0.01) without any change in tissue plasminogen activator (TPA) levels. No changes were noted at 1 week of Max EPA intake in normal subjects, but at 3 weeks serum triglyceride concentrations and PAI-1 levels decreased 32 +/- 13% and 22 +/- 4%, respectively (p less than or equal to 0.02) without change in TPA. The magnitude of reduction in triglycerides was dependent on the initial serum concentration (r = 0.68, p less than or equal to 0.01). In addition, decrease in PAI-1 levels correlated with reduction in serum triglycerides (r = 0.79, p less than or equal to 0.01). This study shows that omega-3 PUFA intake reduces PAI-1 levels without change in TPA antigen. These observations may relate to decrease in thrombotic activity upon consumption of large amounts of fish or fish-derived products.