During exercise, β-feedforward coronary vasodilation has been shown to contribute to the matching of myocardial oxygen supply with the demand of the myocardium. Since both β₁- and β₂-adrenoceptors are present in the coronary microvasculature, we investigated the relative contribution of these subtypes to β-feedforward coronary vasodilation during exercise as well as to infusion of the β₁-agonist norepinephrine and the β₁- and β₂-agonist isoproterenol. Chronically instrumented swine were studied at rest and during graded treadmill exercise (1–5 km/h) under control conditions and after β₁-blockade with metoprolol (0.5 mg/kg iv) and β₁/β₂-blockade with propranolol (0.5 mg/kg iv). The selectivity and degree of β-blockade of metoprolol and propranolol were confirmed using isoproterenol infusion (0.05–0.4 μg· kg⁻¹·min⁻¹) under resting conditions. Isoproterenol-induced coronary vasodilation was mediated through the β₂-adrenoceptor, whereas norepinephrine-induced coronary vasodilation was principally mediated through the β₁-adrenoceptor. Exercise resulted in a significant increase in left ventricular norepinephrine release and epinephrine uptake. β₁-Adrenoceptor blockade with metoprolol had very little effect under resting conditions. However, during exercise, metoprolol attenuated the increase in myocardial oxygen supply in excess of the reduction in myocardial oxygen demand, as evidenced by a progressive decrease in coronary venous Po₂. Consequently, metoprolol caused a clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po₂. Additional β₂-adrenoceptor blockade with propranolol further inhibited myocardial oxygen supply during exercise, resulting in a further clockwise rotation of the relationship between myocardial oxygen consumption and coronary venous Po₂. In conclusion, both β₁- and β₂-adrenoceptors contribute to the β-feedforward coronary resistance vessel dilation during exercise.