To investigate the effect of pre-treatment of a thrombus with a low dose of urokinase on establishing patency in a persistent infarct-related artery (IRA) during direct percutaneous coronary angioplasty (PTCA), the frequency of acute restenosis during direct PTCA, alone, or in combination with the intracoronary administration of urokinase, was examined in a consecutive nonrandomized series of patients with acute myocardial infarction (AMI). Two hundred and seventy-two successful PTCA patients (residual stenosis <50%) were divided into 2 groups: 88 patients received pre-treatment with intracoronary urokinase following PTCA (combination group); 184 received only direct PTCA without thrombolytic therapy (PTCA group). In the present study, after achievement of a residual stenosis of less than 50%, IRA was visualized every 15 min to assess the frequency of acute restenosis, which was defined as an acute progression of IRA with more than 75% restenosis after initially successful PTCA. In the patients with a large coronary thrombus, the frequency (times) of acute restenosis was significantly lower in the combination group than in the PTCA group (0.98+/-0.19 vs 2.92+/-0.32, p<0.0001). On the other hand, in the patients with a small coronary thrombus, the frequency of acute restenosis showed no difference in either group. The present study indicates that in patients with AMI, PTCA combined with pre-treatment of a low dose of urokinase is much more effective than PTCA alone, especially for those patients who have a large coronary thrombus.