The effect of bunitrolol, a beta-adrenergic blocking agent having intrinsic sympathomimetic activity, on ischemic myocardial metabolism was examined in anesthetized dog hearts. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min. Bunitrolol (0.3 or 1.0 mg/kg of body weight) was injected intravenously 5 min before the onset of ischemia. Ischemia reduced myocardial high-energy phosphate levels and changed the levels of glycolytic intermediates. Bunitrolol at a dose of 0.3 mg/kg significantly decreased heart rate, whereas the drug at a dose of 1.0 mg/kg did not. This result suggests that intrinsic sympathomimetic activity is observed only at a high dose of bunitrolol. Pretreatment with bunitrolol at 0.3 but not 1.0 mg/kg attenuated the myocardial metabolic changes caused by 3 min of ischemia. After 30 min of ischemia, a beneficial effect of bunitrolol on the ischemic myocardium was not observed. These results suggest that bunitrolol may lessen the ischemic influence on the myocardium in the early stage of ischemia and that intrinsic sympathomimetic action may not have a beneficial effect on the ischemic myocardium.