In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.