Large and small coronary arteries are subject to control by alpha- and beta-adrenergic mechanisms. However, controversy exists as to the distribution and physiological effects of alpha- and beta-adrenergic receptor subtypes in large coronary arteries. Studies in our laboratory have addressed these questions in conscious calves, chronically instrumented to measure large coronary artery diameter and coronary blood flow. Additionally, adrenergic receptor subtype distribution was determined using ligand binding assays in membrane preparations isolated from large coronary arteries of calves. Physiological results demonstrate, in contrast to the results of most previous studies, that both alpha 1- and alpha 2-adrenergic receptors elicit constriction of the large coronary artery. Studies with ganglionic blockade indicate that the constriction was unaltered by autonomic reflexes or presynaptic release of neurotransmitters. Selective beta-adrenergic receptor activation demonstrated that both beta 1- and beta 2-adrenergic receptors elicit dilation of large coronary arteries, and that the vasodilation was direct, i.e., it was not mediated by increases in coronary blood flow. Biochemical characterization of adrenergic subtype density indicated the presence of both alpha 1- and alpha 2-, as well as beta 1- and beta 2-adrenergic receptor subtypes. Thus, both biochemical and physiological data support the concept that large coronary arteries are regulated by both alpha 1- and alpha 2-, as well as beta 1- and beta 2-adrenergic receptor subtypes.