Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous Streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct survival (ISIS-2). Patients who received Streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p < 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p < 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of Streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease ≥20% is required for identification of salvage. Application of this threshold identified 10 (25%) of 40 control patients and 20 (61%) of 33 patients in the Streptokinase group (p < 0.005). Thus, intravenous Streptokinase significantly changes the relation between predicted and final acute myocardial infarction size, demonstrating the potential of the standard ECG for noninvasive evaluation of myocardial salvage after thrombolytic therapy.