Coronary vessels have β2-adrenergic receptors, but their role in distributing flow across the ventricular wall independently of cardiac metabolic and mechanical factors that influence coronary resistance is unknown. We studied the working heart of open-chest dogs and measured blood flow with radioactive microspheres in four layers across the left ventricular wall before and during β2-receptor activation by intracoronary infusions of salbutamol or isoproterenol. Myocardial β1, receptors were blocked with practolol, and aortic pressure, heart rate, and myocardial oxygen consumption were prevented from changing significantly. β2activation produced a progressively greater increase in flow from the subendocardiumtothe subepicardium with a decrease in the subendocardial:subepicardial (I:O) ratio from 1.40 to 1.00. Coronary resistance decreased progressively from the subendocardium to the subepicardium. To assess the influence on the above results of the transmural redistribution of flow that normally is developed by myocardial contraction in the working heart, similar experiments were conducted in the empty beating heart. A two-step vasodilation with salbutamol decreased the I:O flow ratio from 1.76 to 1.40 and then to 1.27. Coronary resistance decreased from the subendocardium to the subepicardium during both steps of vasodilation. For comparable increments of flow, the decrease in the I:O flow ratio in the empty beating heart was smaller than that in the working heart. These results indicate that the activation of coronary β2receptors redistributes flow toward the subepicardium by producing a larger vasodilation in this region independently of the metabolic and mechanical influences of heart contraction on coronary resistance. This effect is enhanced in the intact heart by the transmural gradient of resistance to flow produced by cardiac contraction.Circ Res 46: 29-36, 1980