The effects and problems of intravenous thrombolytic therapy with a bolus injection of mutant tissue plasminogen activator (t-PA) were investigated in 34 patients with first acute myocardial infarction (AMI). In contrast, 114 patients were selected from 1,003 patients with AMI for treatment using intravenous infusion urokinase (UK). Angiography of these 148 patients revealed a complete occlusion of infarct-related artery with no clear contraindications to the study treatment. With the exception of thrombolysis in myocardial infarction (TIMI-3) recanalization 60 min after a bolus injection of mutant t-PA, the patients were given intracoronary UK in addition to mutant t-PA. The study comparisons were assessed using the following criteria: (1) 60-min assessment of recanalization rates, mutant t-PA vs UK; (2) time interval from initiation of thrombolysis to recanalization, mutant t-PA vs UK; (3) angiographic reocclusion rates within 1 month, mutant t-PA alone vs UK vs mutant t-PA plus UK; and (4) intracerebral hemorrhage rates, mutant t-PA alone vs UK vs mutant t-PA plus UK. There were no significant differences in the recanalization rates between mutant t-PA and UK, but there was a significant reduction in the time to recanalization with mutant t-PA (31.8 +/- 12.7 min) compared with UK (56.5 +/- 6.3 min). There was a significant difference in the reocclusion rates among the 3 treatment groups (20% mutant t-PA alone vs 4% UK vs 0% mutant t-PA plus UK). On the other hand, no significant differences in intracerebral hemorrhage rates among the 3 treatments were observed. In conclusion, thrombolytic therapy with a bolus injection of mutant t-PA achieved more rapid recanalization, but treatment with mutant t-PA led to a high rate of reocclusion.