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Fifty-nine consecutive patients presenting within 6 hours of the onset of symptoms of an acute myocardial infarction were treated with 150 mg of soluble aspirin orally, and either 70 or 100 mg of alteplase divided into 2 intravenous bolus injections separated by 30 minutes. Dosage regimens were either 20 followed by 50 mg (group A), 50 followed by 20 mg (group B), or 50 followed by 50 mg (group C). Coronary angiography 60 minutes after the first bolus showed infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction score 2 or 3) in 13 of 16 (81%) patients in group A, 12 of 17 (71%) in group B, and 10 of 11 (91%) in group C (overall patency rate at 60 minutes: 35 of 44 [80%] patients; 95% confidence interval 68 to 91%). At 90 minutes, patency rates were 15 of 20 (75%) patients in both groups A and B, and 18 of 19 (95%) in group C (overall patency rate 48 of 59 [81%] patients; 95% confidence interval 72 to 91%). Residual thrombus was identified with the 90-minute angiogram in 7 patients in group A, 5 in group B, and 3 in group C. Although there was no statistically significant difference in patency between the 3 dosage regimens at either 60 or 90 minutes there was a trend toward increased patency and more complete thrombolysis at 90 minutes in group C. No episodes of bradyarrhythmia, hypotension or cerebrovascular bleeding were observed after double bolus therapy. There were 7 episodes (12%) of reocclusion, and 3 deaths (5%) within 1-month follow-up. Double bolus alteplase therapy is a convenient and highly effective method of promoting early coronary artery patency.