Pig plasmin (Lysofibrin) was given to 11 patients with phlebographically verified venous thrombosis, 2 of whom were treated two and three times, respectively. The effect on coagulation and fibrinolytic parameters was studied. The platelet count, Owren's P&P (prothrombin plus factors VII and X), plasminogen, factor XIII, and antithrombin III did not change during the treatment. All patients developed a proteolytic activity demonstrable on both unheated and heated fibrin plates. The fibrinogen decreased successively to very low levels, and parallel to this an increase in fibrin/fibrinogen degradation products was found. The factor VIII and factor V activities decreased immediately after each Lysofibrin infusion but normalized rapidly again. The factor VIII molecule, however, retained its reactivity to rabbit antiserum against factor VIII. Immediately after the plasmin infusion a decrease of both alpha2-macroglobulin (alpha2-M) and the rapidly reacting alpha2-antiplasmin was observed. alpha2-M decreased successively and in several of the patients values were unmeasurable for a period of some days. A complex formation between pig plasmin and the alpha2-antiplasmin was demonstrated in crossed immunoelectrophoresis. The complexes were rapidly cleared from the circulation. No interaction between the pig plasmin and the inhibitor of the plasminogen activation, alpha1-antitrypsin or inter-alpha- inhibitor, was found.