This study was designed to evaluate the effects of nitroglycerin and phenylephrine-induced arterial hypertension on regional myocardial blood flow in awake dogs with acute occlusion of the left circumflex coronary artery. Myocardial blood flow to four transmural layers from epicardium to endocardium was estimated with 7-9 micron radionuclide labeled microspheres in 1) the nonischemic myocardium, 2) the central ischemic zone, and 3) the border zone separating ischemic from normally perfused myocardium. Measurements were repeated 1) during infusion of nitroglycerin, 0.015 mg/kg/min, 2) during phenylephrine administered to increase arterial pressure 60 mm Hg above the control measurements, and 3) during combined nitroglycerin and phenylephrine administration. Both nitroglycerin and phenylephrine increased myocardial blood flow to the central ischemic area; nitroglycerin significantly decreased the resistance of the collateral vascular system, while the increased flow during phenylephrine administration was accounted for entirely by the increased arterial pressure with no change in collateral vascular resistance. The increased blood flow to the central ischemic zone during nitroglycerin administration was delivered preferentially to the subendocardium while the increased blood flow during phenylephrine administration was directed exclusively to the subepicardium. Neither nitroglycerin nor phenylephrine significantly altered computed vascular resistance of the border zone, but because of the increased driving pressure, blood flow to the border zone was significantly increased during phenylephrine administration.