Rapid and complete reperfusion is important for the reduction of infarct size and mortality in acute myocardial infarction. The optimum reperfusion therapy with regard to the recanalization rate and the time elapsing between onset and complete reperfusion was evaluated. One hundred fifty-four patients with total occlusion of the infarct-related artery within 6 hours of the onset were classified into four therapy groups: PTCA group (n = 58) undergoing primary percutaneous transluminal coronary angioplasty (PTCA), t-PA-IC group (n = 44) receiving tissue plasminogen activator (t-PA) intracoronary infusion, t-PA-IV group (n = 14) receiving intravenous t-PA infusion, and mt-PA-IV group (n = 38) receiving intravenous mutant t-PA infusion. Although the recanalization rate was high in the PTCA group, there were no differences between the four groups as a supplement to immediate or rescue PTCA. The time elapsing between initiation of thrombolysis and complete reperfusion was shorter in the mt-PA-IV group than in the t-PA-IV group. Assuming the time from hospital arrival to initiation of intravenous thrombolysis was 20 min, the recanalization rate at 60 min after arrival in hospital was higher in the mt-PA-IV group than the PTCA and t-PA-IC groups. Although additional coronary angiography and PTCA may be required to improve the low recanalization rate compared with primary PTCA, intravenous infusion of mutant t-PA was the most promising therapy to achieve early reperfusion.