Adriamycin, an anthracycline antibiotic, which is used in the treatment of various tumors, is known to cause severe cardiomyopathy. The present study examined the protective effects of Picrorhiza kurroa, an ayurvedic medicinal plant, on myocardial antioxidant defense system in adriamycin-induced cardiomyopathy in rats. Intraperitoneal administration of adriamycin (1.5 mg/kg body weight/ day, i.p. for 15 days) caused significant rise in the levels of diagnostic marker enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phoshokinase (CPK)] in plasma and lipid peroxidation in the heart tissue of experimental rats. Concomitant decline in the level of reduced glutathione (GSH) and the activities of glutathione-dependent antioxidant enzymes (GPx and GST) and antiperoxidative enzymes (SOD and CAT) in the myocardial tissue were also observed. Oral administration of P. kurroa extract (50 mg/kg body weight/day, for a period of 15 days) significantly prevented all these adriamycin-induced adverse effects and maintained the rats at normal status. The protective effect of P. kurroa might be ascribable to its membrane-stabilizing property and/or antioxidant nature.