Early focal myocardial lesions in rats induced by five cardiotoxic compounds were histopathologically observed 1 hr and 4 hr after a single intravenous injection with 1/10 LD50 and LD50. The lesions were observed 1 hr and 4 hr after the treatment with LD50 of isoproterenol (ISP), 4 hr with 1/10 LD50 of ISP, 4 hr with LD50 of hydralazine (HYD), caffeine (CAF) and cyclophosphamide (CYC), but not with adriamycin (ADR). The lesions consisted of homogeneously intensely eosinophilic staining, contraction band formation and fragmentation of cardiac muscle fibers. The lesions were interspersed in the inner one third of the left ventricular walls including the papillary muscles with ISP, HYD and CAF, and were all over the ventricular myocardium with CYC.