The effects of recombinant tissue plasminogen activator (rt-PA) and urokinase on patency and early reocclusion of infarct-related coronary arteries were investigated in a single blind, randomized multicenter trial in 246 patients with acute myocardial infarction of less than 6 h duration. Both 70 mg of single chain rt-PA with an initial bolus of 10 mg and 3 million units of urokinase with an initial bolus of 1.5 million units were given intravenously over 90 min. The first angiographic study at the end of the infusion revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 69.4% of 121 patients given rt-PA versus 65.8% of 117 patients given urokinase (p = NS). Among patients treated within 3 h from symptom onset a patent infarct-related artery was found in 63.9% of 72 patients given rt-PA versus 70% of 70 patients given urokinase (p = NS). There were five cardiac deaths in each group and one fatal intracranial hemorrhage in the rt-PA group. The in-hospital reinfarction rate was 8.9% versus 13.2% for patients treated with rt-PA and urokinase, respectively. There was no difference in left ventricular function at baseline and follow-up catheterization studies. Both drugs were well tolerated and there was no significant difference in cardiovascular or bleeding complications between the two groups. It is concluded that rt-PA and urokinase in the dosages used provide similar efficacy and safety in the treatment of acute myocardial infarction. Reocclusion during the first 24 h may be less frequent after urokinase treatment.