Forty-two patients with acute myocardial infarction received 150-mg recombinant human tissue-type plasminogen activator (rt-PA) at 2.3 ±1.2 hours after the onset of chest pain. After a 40 U/kg bolus of heparin, rt-PA was given as a 10-mg bolus followed by a 2-hour continuous infusion of 90 mg in the first hour and 50 mg in the second hour. Non-angiographic signs of reperfusion occurred during treatment (41 ± 21 minutes) in 35 patients and in 1 other patient about 30 minutes after rt-PA. Three patients had discordant nonangiographic signs of reperfusion, 2 patients had no evidence of reperfusion and 1 patient in cardiogenic shock died before completion of the rt-PA infusion and before reperfusion status could be ascertained. Clinical signs of early reocclusion occurred in 4 of the 36 patients with evidence of reperfusion, 3 of whom were retreated with rt-PA with clinical success in 2. Coronary angiography 10 ± 8 hours later revealed a patent artery of infarction in 35 patients: 32 with nonangiographic signs of sustained reperfusion, both patients with successfully treated reocclusion and 1 of 3 patients with discordant signs of reperfusion. Angiography revealed evidence of partial reperfusion in the remaining 2 patients with discordant signs, and an occluded artery was found in both patients without any evidence of reperfusion and in both patients with clinical signs of persistent reocclusion. Hemorrhagic complications occurred in 9 patients, 7 were related to procedural trauma and 2 patients required a blood transfusion. Four patients died, each of a cardiac cause: 3 in hospital and 1 at home. These data suggest that a 2-hour intravenous infusion of 150-mg rt-PA achieves a high rate of reperfusion in patients with acute myocardial infarction without high incidence of reocclusion or serious bleeding.