Prophylactic effects of sulfinpyrazone (100 mg/Kg), aspirin (5 mg/Kg, 50 mg/Kg), and propranolol (2 mg/Kg, 10 mg/Kg) on myocardial necrosis and hypertrophy induced by isoproterenol were examined. Drugs were administered to rats daily by gavage for a period of 2 weeks and after that isoproterenol (40 mg/Kg) was injected subcutaneously. The control group received gavage of water and isoproterenol injection. The "no infarct" group received gavage of water and saline injection. Premedication of sulfinpyrazone and propranolol significantly preserved myocardial CK activity and decreased cardiac hypertrophy compared with control group (24 hours after isoproterenol injection) while aspirin did not have such effects. Myocardial cyclic AMP concentration significantly increased 30 min after isoproterenol injection in control and all the premedicated rats compared with the "no infarct" rats. The increment of cyclic AMP was not suppressed by sulfinpyrazone and propranolol during this period. Plasma levels of prostaglandins were significantly suppressed by the administration of sulfinpyrazone and 50 mg/Kg of aspirin, and were not suppressed by 5 mg/Kg of aspirin. It was concluded that premedication of sulfinpyrazone and propranolol reduce cardiac necrosis and hypertrophy induced by isoproterenol, but aspirin did not have such cardioprotective effects.