The effect of pretreatment with intravenous infusion of Streptokinase (SK) (16,700 U/min for 90 minutes), started after diagnosis and followed by intracoronary application (2000 U/min) (protocol 1), was assessed retrospectively in 55 consecutive patients with acute transmural myocardial infarction (MI). Another 46 patients with acute Ml treated previously by intracoronary thrombolysis served as control subjects (protocol 2). Reperfusion at first coronary injection was observed after pretreatment in 25 patients (45%), but in no control patient (p <0.001). Fifteen patients with successful pretreatment (group A), 20 patients with successful treatment according to protocol 2 (group B) and 9 patients with unsuccessful thrombolysis (group C) were restudied after 4 weeks. Data from patients with reinfarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty before restudy were excluded. Thallium-201 scintigraphy was performed before and 24 hours after treatment, serum creatine kinase activity was measured every 8 hours for 3 days and regional ejection fraction (EF) of acute Ml was determined before and 4 weeks after treatment. The scintigraphic, enzymatic and hemodynamic data before treatment indicated severe and comparable ischemia among the 3 groups. The thallium-201 perfusion defect decreased in group A (from 41 to 21 %, p < 0.01) and in group B (from 38 to 26%, p < 0.01), but did not change in group C (from 37 to 31 %, difference not significant). Peak serum creatine kinase levels normalized by the perfusion area of acute Ml was 20, 33 and 58 U/liter unit in groups A, B and C. The mean values of groups A and C were significantly different (p < 0.01). The regional ejection fraction of acute MI recovered after 4 weeks in group A (from 24 to 42%, p < 0.001), but not in groups B or C. Time to catheterization from onset of symptoms was similar among the 3 groups; however, start of treatment and angiographic proof of reperfusion (3.5 vs 4.5 hours, p < 0.05) was achieved earlier in group A than in group B. Pretreatment with intravenous infusion of SK was followed by reperfusion of acute Ml in 45% of patients. After 4 weeks, successfully pretreated patients revealed less severe ischemic damage than that in patients treated successfully by intracoronary infusion of SK alone.