Fifteen patients who arrived between 6 and 24 hours after the onset of acute myocardial infarction and who were found to have totally occluded coronary arteries, received aspirin, heparin, and tissue plasminogen activator given over 3 hours. Eight patients were randomly assigned to receive intravenous prostaglandin E1, 20 ng/kg/min for 6 hours, while seven patients received placebo infusion. Coronary arteriography begun immediately before the start of tissue plasminogen activator and repeated every 15 minutes revealed restoration of antegrade flow in two of eight (25%) patients treated with prostaglandin E1 and in two of seven (28%) patients receiving placebo. Pharmacologic sampling of tissue plasminogen activator levels were performed at baseline and 30, 45, 60, 75, 90, 135, 180, 190, 210, and 240 minutes afterwards for assessment of tissue plasminogen activator antigen. There was no difference in fibrinogen levels and no difference in tissue plasminogen activator antigen levels at these time periods. Clearance values of tissue plasminogen activator were calculated and were not different between the two groups. These data do not support the use of prostaglandin E1 for the acceleration of reperfusion in patients receiving tissue plasminogen activator for acute myocardial infarction.