As a result of gradual coronary occlusion, coronary collaterals are stimulated to develop. This maturation process involves not only dilatation of the vessel, but the development of new vascular smooth muscle. Experiments have been performed to examine vasomotor characteristics of mature coronary collaterals from dogs 3 to 6 months following ameroid constrictor placement. Studies in Langendorff blood-perfused hearts have shown that transcollateral resistance does not change during either the administration of alpha 1- or alpha 2-adrenergic agonists. Isolated collateral vessels studied as rings in organ chambers do not constrict to either alpha 1- or alpha 2-adrenergic agonists. These studies show that mature collateral vessels are not likely to possess functioning alpha-adrenergic receptors. Subsequent experiments using a cover slip autoradiographic ligand-binding approach have demonstrated a population of beta-adrenergic receptors on mature coronary collaterals. Studies of isolated collaterals have demonstrated beta-adrenoceptor-mediated relaxation that appears due to a population of mixed beta 1- and beta 2-adrenergic receptors. Subsequent studies have demonstrated that mature collateral vessels are hyperresponsive to the vasoconstrictor effects of vasopressin and that concentrations of vasopressin which may be encountered in pathophysiologic conditions can markedly attenuate coronary collateral perfusion. Finally, the microcirculation of the collateral-dependent myocardium develops endothelial cell dysfunction. This results in impaired endothelium-dependent relaxations to adenosine diphosphate and acetylcholine and enhanced vasoconstriction to vasopressin. These alterations of the coronary circulation may have important implications regarding neurohumoral regulation of myocardial perfusion in collateral-dependent myocardium.