This study tested whether diabetes mellitus impairs coronary blood flow control sufficiently to alter the balance between myocardial oxygen delivery and metabolism. Dogs (n = 7) were instrumented with catheters in the aorta and coronary sinus, and with a flow transducer on the circumflex coronary artery. Coronary blood flow, myocardial oxygen consumption (MVO2), heart rate and aortic pressure were measured at rest and during treadmill exercise before and after induction of diabetes with alloxan monohydrate (40 - 60 mg/kg). Arterial plasma glucose concentration increased from 4.6+/-0.2 mM in non-diabetic, control dogs to 20.2+/-2.3 mM one week after alloxan injection. In non-diabetic control dogs, exercise increased MVO2 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.4-fold. Coronary venous PO2 decreased from 19.4+/-0.6 mmHg at rest to 14.7+/-0.7 mmHg during exercise. Diabetes significantly attenuated exercise coronary hyperemia and reduced coronary venous PO2 at rest (15.6+/-0.5 mmHg) and during exercise (12.6+/-0.8 mmHg). Diabetes also significantly reduced myocardial oxygen delivery at each level of exercise. Acute hyperglycemia alone did not alter exercise-induced coronary vasodilation or reduce coronary venous PO2. These findings demonstrate that experimental diabetes attenuates functional coronary hyperemia and impairs the balance between coronary blood flow and myocardial metabolism. However, this deleterious effect is not related to acute hyperglycemia but to the chronic disease process of diabetes mellitus.