The purpose of this study was to determine whether streptokinase exacerbates intramyocardial hemorrhage during coronary reperfusion, has any intrinsic effect on myocardial infarct size other than its ability to lyse proximal thrombi in coronary arteries, and can abolish the no-reflow phenomenon. Anesthetized open-chest dogs underwent coronary occlusion for 3 hr followed by 3 hr of reperfusion. Area of infarct was assessed by tetrazolium staining, anatomic zone of no-reflow by injection of the fluorescent dye thioflavin S at the end of the reperfusion period, regional blood flow during occlusion and reperfusion by the radioactive microsphere technique, and extent of gross hemorrhage by assessment of photographic enlargements of the heart slices. Area of infarction of the left ventricle was similar in control (13.4 +/- 3.6%) and streptokinase-treated dogs (13.0 +/- 2.9%; p = NS). Seven of eight dogs in the untreated group had anatomic perfusion defects as assessed by thioflavin S at the end of the reperfusion phase; seven of eight dogs in the streptokinase group had anatomic perfusion defects. There was no difference in the extent of gross hemorrhage between the two groups (6.5 +/- 2.1% of left ventricle in controls and 5.7 +/- 2.3% in streptokinase-treated dogs). Severe depression of regional blood flow during reperfusion was present within the infarcted tissue and was associated with an anatomic perfusion defect as defined by thioflavin S; there was moderate depression of flow within the noninfarcted, salvaged subepicardium. In a separate series of experiments, infarcts were assessed for hemoglobin content. Intramyocardial hemoglobin levels were not higher after fibrinolytic therapy plus reperfusion compared with reperfusion alone.(ABSTRACT TRUNCATED AT 250 WORDS)