The optimal therapeutic regimen for t-PA in humans remains to be determined. The ideal dosage regimen for t-PA should achieve effective thrombolysis as quickly as possible with minimum fibrinogenolysis to minimize bleeding. Our findings in rabbits suggest that the present regimens in humans might be improved by using frequent rapid infusions rather than the more prolonged infusions. Clearly, the results of our animal studies will have to be confirmed in man before firm recommendations can be made.