We have shown that streptokinase (SK) is capable of building up thrombi in vivo on the blood-superfused collagen strips in extracorporal circulation of anaesthetized cats. The thrombogenic effects of SK appeared in all animals, irrespectively of whether SK was administered as intravenous bolus injections or infusions at doses comparable to those used for the treatment of patients with acute myocardial infarction. The thrombogenic phase of SK lasted up to 1.5 h and was followed by expected thrombolytic phase. Both phases were mediated by generation of plasmin. Inhibition of cyclooxygenase by aspirin or nitric oxide synthase by NG-nitro-L-arginine did not prevent SK from being thrombogenic. Also nitric oxide donor-SIN-1 did not remove the formation of thrombi by SK. The only effective treatment consisted of complementing the SK therapy with exogenous prostacyclin-like activity (e.g. iloprost). Prostacyclin not only abolishes thrombogenesis by SK but it also intensifies its thrombolytic action.