The clinical benefit of streptokinase (SK) in the treatment of patients with acute myocardial infarction may be influenced by effects other than myocardial reperfusion per se. Polymorphonuclear leucocytes (PMNs) have been hypothesized to participate in the process of reperfusion injury in the postischemic myocardium. The purpose of the present study was therefore to investigate the effect of SK on human PMN function in vitro, and ex vivo in patients with acute myocardial infarction. SK was not in itself chemotactic to PMNs, and preincubation with SK did not alter the chemotactic response of PMNs to formyl-Met-Leu-Phe (FMLP) or zymosan-activated serum. However, incubation of fresh citrated plasma with SK resulted in the generation of chemotactic activity, and this effect was dependent on complement activation by SK. In experiments with PMNs from 20 health donors, preincubation of plasma and SK, followed by incubation with PMNs, primed the cells for enhanced chemiluminescence response to FMLP. The PMN priming by SK+plasma showed considerable interindividual variation, and was not mediated by a direct action of plasmin on PMNs. In 10 patients with acute myocardial infarction treated with SK, a reduction in superoxide production by PMNs was observed immediately following SK. The results suggest that SK modulates human PMN function in vivo, and these effects may influence the therapeutical value of this agent.