There is increasing evidence that elevated plasma levels of hemostatic factors [fibrinogen, factor VII, von Willebrand factor, fibrin D-dimer, and tissue plasminogen activator (t-PA) antigen] are independently linked to risk for coronary heart disease (CHD). Women with polycystic ovary syndrome (PCOS) are insulin-resistant and have increased risk for CHD and type 2 diabetes, but there are few data on hemostatic markers in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index (BMI) were recruited. Insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique. Factor VIIc was determined by a clotting assay; fibrinogen was determined by nephelometry; and t-PA, D-dimer, and von Willebrand factor antigens were measured by ELISA techniques. Of these hemostatic markers, only t-PA concentration was significantly (P = 0.013) elevated in women with PCOS relative to controls. t-PA correlated with BMI in both PCOS and controls (r = 0.428, P < 0.1; and r = 0.686, P < 0.01) and inversely with the insulin sensitivity index (r = -0.590, P < 0.05; and r = -0.620, P < 0.05, respectively). After further adjustment for BMI and insulin sensitivity, there remained a significant difference in t-PA between cases and controls (P = 0.017). Together, age and insulin sensitivity explained 39% of the variance in t-PA in women with PCOS (P < 0.05). Total testosterone did not correlate significantly with t-PA in either group. We conclude that women with PCOS have significantly increased t-PA concentrations relative to women with normal menstrual rhythm and normal androgens. We suggest that elevated t-PA and dysfibrinolysis may be a factor in the increased cardiovascular morbidity seen in PCOS.