To delineate electrocardiographic similarities and differences in ventricular depolarization between left posterior fascicular block and posteroinferior myocardial infarction, these lesions were produced in two and three stage experiments in dogs and baboons. The observed QRS changes of left posterior fascicular block were found to be immediate, little influenced by healing of the acute lesion, and partially correctable by pacing viable myocardium distal to the block. In contrast, the QRS changes of posteroinferior myocardial infarction occurred later with cicatrization and were essentially unaffected by pacing. The intrinsic deflection in direct posterior epicardial leads was more delayed by left posterior fascicular block than by posteroinferior myocardial infarction. Both lesions accounted for Q waves in leads II, III and aVF. However, R amplitude in these same leads was increased after left posterior fascicular block but decreased after posteroinferior myocardial infarction. The mean QRS axis in the frontal plane was shifted toward the vertical in left posterior fascicular block but little changed or shifted slightly away from the vertical in posteroinferior myocardial infarction. When left posterior fascicular block and posteroinferior myocardial infarction coexist, there may be masking, imitation or enhancement of the effects of one lesion by the presence of the other. To assist in recognition, distinguishing features are described.