Thrombolytic therapy has been documented to result in reperfusion of jeopardized myocardium and reduction in the size of the acute myocardial infarction (AMI). The effect of intravenous streptokinase on a creatine kinase-MB (CK-MB) reperfusion index and an ECG estimate of myocardial salvage was therefore studied in 65 patients with a first AMI, randomized to treatment with streptokinase (n = 33) or placebo (control group, n = 32). Reperfusion was defined as a CK-MB appearance rate constant (k1) > 0.185. The final AMI size was first predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. The final AMI size was estimated from the QRS score on the predischarge ECG. Myocardial salvage was defined as a ≥20% decrease from predicted to final AMI size. The k1 value in the control group was significantly lower than that in the streptokinase group (median 0.157 versus 0.328; p = 0.0001). Accordingly the reperfusion rate was higher in the streptokinase group than in the control group (88% versus 34%; p = 0.0002). The difference in AMI size (final-predicted) was significantly greater in the streptokinase group than in the control group (median -7% versus +1%; p = 0.0001). Myocardial salvage occurred in 60% and 19%, respectively (p = 0.004). A significant correlation was found between CK-MB reperfusion and ECG salvage: 19 of 20 streptokinase-treated patients with salvage also had reperfusion. Despite similar reperfusion rates among patients randomized to treatment with streptokinase early (≤4 hours) and late (5 to 12 hours) after the onset of symptoms, the patients treated earller had a significantly greater difference in AMI size (median -11% versus -3%; p = 0.02). The 19 patients identified in the streptokinase group as having both myocardial reperfusion and salvage showed a trend toward a lower two-dimensional echocardiographic wall motion score than the 14 patients having either or none (median 11 versus 22; p = 0.17), indicating more preserved left ventricular function. Thus, serial CK-MB and ECG analysis in patients with AMI undergoing thrombolytic therapy provides a noninvasive means for assessing therapeutic success.