Since coronary thrombosis is a principal factor in the evolving necrotic process in the majority of patients with acute myocardial infarction (AMI), a prospective study was conducted in 25 AMI patients who underwent expeditious coronary arteriography. Of these patients, 22 with totally occluding thrombus also received early streptokinase (STK) administration. STK was given by intracoronary (20 patients) or systemic (two patients) infusion, 2000 to 50,000 IU/min, to a total dose of 125,000 to 500,000 IU within 10 hours of AMI symptom onset. Eighteen patients had angiographically visualized successful coronary thrombolysis; the shorter the interval between onset of symptoms to treatment, the more rapid was the clot dissolution. Successful thrombolysis occurred concomitantly with readily managed reperfusion ventricular tachyarrhythmias in nearly all patients. In addition, STK recanalization resulted in relief of ongoing chest pain in 10 of 12 patients, 10 of 16 evidenced immediate normalization of hyperacute ST segment abnormalities, and 8 of 14 demonstrated subsequent improvement of angiographically visualized left ventricular (LV) ejection fraction. In the percutaneous transluminal coronary recanalization (PTCR) procedure, the step of using a soft-tipped guide wire itself was transiently useful in only one of seven patients in whom this was attempted; reocclusion took place without added STK therapy. Nitroglycerin (NTG) alone produced only slight distal patency in but 1 of 19 patients with coronary occlusion given the nitrate. Importantly, in 14 control AMI patients receiving conventional treatment without STK, 10 showed angiographically complete occlusion of the coronary artery supplying the infarct region 1 month after infarction, thereby excluding spontaneous clot lysis mimicking STK-PTCR-induced reperfusion. These data support the concept that coronary occlusion by thrombosis is inherently involved with AMI and that rapid PTCR application of intracoronary STK provides potent thrombolysis, superior to that provided by NTG and guide wire passage in reestablishing coronary flow with attendant salvage of jeopardized myocardium and with subsequently improved LV function.