Summary1. The concentration of the major components of the fibrinolytic enzyme system was compared in venous and arterial blood samples from male subjects.2. The plasminogen activator concentration was higher in venous blood and the arterio-venous difference increased as its concentration rose, but the ratio of the arterial to venous level remained constant.3. No arterio-venous difference was found for anti-urokinase activity, antiplasmin, plasminogen and fibrinogen.4. It is concluded that venous blood determinations of the components of the fibrinolytic enzyme system reflect satisfactorily arterial blood levels.

Summary1. The plasminogen content of serum and plasma does not differ. The serum remaining after the production of an in vitro artificial thrombus has a plasminogen content similar to the original plasma. Direct measurement of the plasminogen content of artificial thrombi confirms that little plasminogen is adsorbed onto fibrin during the process of clotting.2. The lysis of pre-formed artificial thrombi by urokinase is substantially increased in the presence of plasma. This is not due to free plasmin in the medium surrounding the thrombus.3. Partially purified plasminogen is adsorbed onto artificial thrombi endowing them with the capacity to lyse on the addition of urokinase. In contrast plasminogen from plasma or serum is not adsorbed onto thrombi.4. We suggest that the lysis of a thrombus results from diffusion of circulating plasminogen into the thrombus and its interaction with activator on the surface of the fibrin fibrils with consequent plasmin formation.

Summary1. Protease I was found to have potent fibrinolytic activity in concentrations which exceeded the blood inhibitory capacity when tested on fibrin plates and artificial thrombi.2. Plasma inhibited the proteolytic activity of protease I to a greater extent than serum; serum had a greater inhibitory effect on protease I than on plasmin. Trasylol did not inhibit the proteolytic action of protease I.3. Protease I caused the slow formation of fibrin in plasma in concentrations which did not produce fibrinogenolysis; this effect was seen in Al(OH)3-adsorbed plasma, and was not inhibited by heparin. Protease I also shortened the recalcified plasma clotting time.4. The fibrinogenolytic action of protease I was more rapid than its fibrinolytic action both in the presence and absence of plasma inhibitors. No concentration of protease I lysed fibrin in plasma without prior destruction or conversion to fibrin of the surrounding plasma fibrinogen.5. It is concluded from these in vitro studies that protease I does not have the properties necessary for a satisfactory thrombolytic agent.

Summary1. The extent of lysis of artificial thrombi by urokinase is dependent on their fibrin content and on the plasminogen concentration of the plasma from which they are made.2. The lysis of thrombi in the presence of plasma increases with increasing concentrations of urokinase, but very high urokinase concentrations are inhibitory to thrombolysis.3. It is postulated that incomplete thrombolysis is due to insufficient plasmin formation within the thrombus, but that plasminogen-containing plasma can diffuse into a thrombus allowing lysis to continue until complete dissolution.