The effects of i.v. and intracoronary (i.c.) nitroglycerin, i.v. propranolol, and the combination of propranolol and nitroglycerin on myocardial oxygen consumption (MVO2) and lactate utilization were studied in situ ischemic working dog hearts. I.v. nitroglycerin reduced MVO2 9% which was associated with the peripheral vasodilatory actions of the drug. I.c. nitroglycerin which had no detectable effects on the peripheral vasculature had no significant effect on MVO2. I.v. propranolol caused an 8% reduction in MVO2 and this action was associated with a negative chronotropic and a slight negative inotropic effect. However, the combination of propranolol and nitroglycerin which was more effective than either drug alone, reduced MVO2 18% thereby indicating that the effects of the two drugs on oxygen consumption are additive. These results support the concept that the reduction of MVO2 seen with nitroglycerin is principally due to peripheral vasodilatory actions of the drug while that seen with propranolol is due to that drug's effect on the heart and the effects of the two agents are complementary.