The utilization of streptokinase as a thrombolytic agent is prevalent in the management of patients following a myocardial infarction. The present investigation was designed to assess the direct effects of streptokinase infusion on the normal isolated rat heart and on the globally ischemic isolated rat heart. The effects of streptokinase on the mechanical function of the hearts were monitored, as well as the effects on the membrane integrity of the cells, as indicated by enzyme release. The normal hearts were infused with either buffer or streptokinase. Both the normal and streptokinase-treated normal hearts exhibited a decrease in function during the course of each experiment. Under these conditions, there were no significant differences in the values for mechanical function in either group. The release of lactate dehydrogenase (LDH) and creatine kinase (CK) into the coronary effluents was not significantly increased during the infusion of streptokinase. There was a significant increase in the release of nucleosides during the streptokinase infusion period compared with the buffer infusion period. The infusion of either buffer or streptokinase was compared in the preischemic and postischemic rat heart. The values obtained during preischemic infusion with buffer or streptokinase were comparable to the values obtained in the normal and streptokinase-treated normal hearts. There were no significant differences in the values for mechanical function measured during buffer infusion following ischemia compared with those measured during streptokinase infusion following ischemia. In the postischemic hearts, there was a sixfold increase in the release of nucleosides during buffer infusion, whereas only a twofold increase was observed in the postischemic hearts during streptokinase infusion. The LDH and CK release during buffer infusion of the postischemic hearts was approximately double the release of those enzymes from the streptokinase-infused postischemic hearts. The enzyme release in the postischemic hearts was severalfold higher in each group than in the comparable normal group. There were no deleterious effects of streptokinase under the conditions of the present study. In fact, there was an indication that streptokinase may offer a protective effect on the ischemic myocardium. © 1984 Raven Press, Ltd., New York.