The effect of exercise on the severity of isoproterenol-induced myocardial infarction was studied in male rats. Ninety-three rats were randomly divided into three groups. The exercise-isoproterenol (E-1) and exercise control (EC) groups exercised daily for thirty days on a treadmill at 1 mph, 2% grade while animals of the sedentary-isoproterenol (S-I) group remained sedentary. Eight animals were assigned to the sedentary control (SC) group which remained sedentary throughout the experimental period. Forty-eight hours after the final exercise period, S-I and E-I animals received a single subcutaneous injection of isoproterenol (250 mg/kg body weight). Animals of the S-I group exhibited significantly (Pp less than 0.05) greater mortality from the effects of isoproterenol than animals of the E-I group. Serum CPK activity for E-I animals was significantly (p less than 0.05) greater than for animals in the S-I and EC groups twenty hours following isoproterenol injection. No statistically significant differences were observed between the two isoproterenol treated groups for severity of the induced lesions, changes in heart weight, or heart weight to body weight ratios. The results indicated that exercise reduced the mortality associated with the effects of large dosages of isoproterenol but had little on the severity of the infarction.