Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia. Of 255 consecutive patients with acute myocardial infarction, 111 were eligible for attempted late thrombolysis. They were randomly assigned to either thrombolytic and antithrombotic treatment (treatment group) or routine treatment (control group). Patients in the treatment group received streptokinase initiated late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3 months. Patients were examined clinically and by bicycle ergometry on discharge from the hospital and after 3 and 12 months. The two groups did not differ with respect to deaths or reinfarctions. There was a trend toward a lower incidence of angina pectoris in the treatment group. Exercise tolerance in this group was significantly higher than in the control group (at 3 months 124 +/- 39 W vs 107 +/- 41 W; p less than 0.05). The difference was entirely accounted for by patients with no previous history of infarction or angina pectoris (at 3 months 142 +/- 37 W vs 112 +/- 45 W; p = 0.01). ECG signs of myocardial ischemia, silent or symptomatic, occurred at significantly lower levels of exercise among patients in the control group compared with patients in the treatment group. The results support the notion that thrombolytic therapy given as late as 12 to 49 hours after the onset of symptoms may reduce the incidence of residual ischemia during the postinfarction period. 