The use of OCAs has been associated with multiple hemostatic abnormalities and an increased risk of thromboembolic disease. These changes have been attributed to increased synthesis of various clotting factors and decreased titers of antithrombin III. Paradoxically, enhanced in vitro fibrinolytic activity is also found in plasmas of women using OCAs. The present study demonstrates marked elevation of both procoagulant and antigenic HF titers in plasmas of women using OCAs, accompanied by a simultaneous decrease in plasma C-1-INH concentration. Titers of plasma prekallikrein, HMW kininogen, PTA, and alpha 2-Pl were unchanged. The rate of kaolin-assisted fibrinolysis was related directly to the titer of HF and inversely to C-1-INH concentration. Further, the addition of human HF to normal plasma enhanced fibrinolytic activity to a degree similar to that observed in plasmas of women taking OCAs. These data suggest that the increase in plasma HF concentration may participate in the phenomenon of enhanced in vitro fibrinolysis associated with OCA use, possibly augmented by diminished inhibitory control by C-1-INH. The relationship of these phenomena to the increased incidence of thrombosis is not known.