To achieve reperfusion early, an intravenous bolus of 2 million units of urokinase was administered in 50 patients with transmural acute myocardial infarction (AMI) 1.8 +/- 2.5 hours after the onset of symptoms. Coronary angiography performed 1.1 +/- 0.6 hours after urokinase therapy revealed patent coronary arteries in 30 patients (60%), with no significant difference between those with anterior and those with inferior AMI. Reocclusion occurred in only 1 of 24 patients restudied. Failure to achieve reperfusion was not related to the degree of systemic fibrinolytic activity, which was equally high in patients who did and those who did not achieve reperfusion, as evident from serially obtained fibrinogen measurements (77 +/- 52 vs 84 +/- 24 mg/dl, difference not significant). Plasmin activity, measured serially from 15 minutes to 24 hours after urokinase in 7 patients, was maximal at 15 minutes and undetectable after 3 hours. Wall motion at the infarct site measured from contrast ventriculograms was significantly better at follow-up only in patients in whom reperfusion was achieved and who received urokinase within 2 hours after the onset of symptoms as compared with patients in whom reperfusion was not achieved (-1.2 +/- 1.4 vs -2.4 +/- 0.9 standard deviations from normal, p less than 0.05). Peak serum creatine kinase level was significantly lower in patients in whom reperfusion was achieved than in those in whom it was not or those who had rethrombosis (802 +/- 763 vs 1,973 +/- 1,071 U/liter, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)