The effects of human tissue-type plasminogen activator (t-PA) on thrombosis were investigated in rabbits. A venous thrombosis model was used for comparison of effects between 70000 IU/Kg of t-PA and 70000 IU/Kg of urokinase (UK). A thrombus was formed around a silk thread in jugular vein and then t-PA purified from the culture fluid of human fibroblast cell line (IMR-90) was infused locally and systemically. The local infusion of t-PA showed a greater thrombolysis than that of UK. Thrombolytic rates of t-PA and UK infusion group were 72.2% and 43.5%, respectively. UK caused the elevation of FDP and the decrease of fibrinogen, plasminogen and α2-antiplasmin in the plasma. On the contrary, these hemostatic parameters of the animal infused with t-PA scarcely changed. These results indicate that t-PA can induce specific thrombolysis without disseminated activation of the fibrinolytic system as compared with UK. The disappearance of t-PA activity in euglobulin fraction was very rapid after the completion of infusion. T-PA has a broader safety margin and greater potential as a thrombolytic agent than UK.