The effect of streptokinase on hemostasis was studied by direct observation of hemostatic plugs in the rabbit mesentery. Infusion of streptokinase did not produce dissolution of hemostatic plugs which were already formed. It did cause a delay in the formation of a platelet mass capable of arresting bleeding from injured vessels. In contrast to systemic infusion, topical application of streptokinase did produce disruption of hemostatic plugs which were already formed. Comparison of the electronmicroscopic appearances of plugs from the control and streptokinase infused animals revealed a lack of fibrin around the plugs in the streptokinase treated animals but no significant difference in platelet morphology. In vitro tests with ADP, thrombin and collagen on platelet-rich plasma from the streptokinase infused animals did not show any difference in platelet aggregation between the pre-and postinfusion samples, even though streptokinase infusion produced a marked increase in plasma fibrinolytic activity. It is suggested that streptokinase infusions, which produce only a slight fall in the plasma fibrinogen level, impair hemostatic plug formation by digestion of fibrin as it is formed around the aggregated platelets.