Experiments were performed on 14 fentanyl-pentobarbital-anesthetized dogs to assess changes in myocardial oxygen supply/demand relations during intravenous infusions of phenylephrine (2.8 micrograms.kg-1.min-1). Myocardial blood flow was measured with radioactive microspheres. Myocardial oxygen and lactate extraction were determined. Myocardial oxygen consumption was calculated with the Fick equation. In series 1, measurements were obtained during phenylephrine-induced pressor responses. In series 2, measurements were obtained with aortic pressure maintained constant with an extracorporeal reservoir during phenylephrine infusion, so that coronary vasomotor responses could be assessed in the absence of increases in ventricular afterload and perfusion pressure. In series 1, the phenylephrine-induced increase in mean aortic pressure (+42%) was accompanied by proportional (60%) increases in myocardial blood flow and myocardial oxygen consumption and with no change in the endocardium-to-epicardium flow ratio, oxygen extraction, coronary sinus oxygen tension and oxygen saturation, or myocardial lactate extraction. In series 2, phenylephrine infusion caused a transmurally uniform 15% decrease in myocardial blood flow combined with a 10% decrease in myocardial oxygen consumption. The coronary arteriovenous oxygen difference increased modestly (+5%), resulting in small decreases in coronary sinus oxygen tension and oxygen saturation, whereas lactate extraction was unaffected. The present findings suggest that phenylephrine has a direct vasoconstrictor effect in the coronary circulation that is weak and completely overridden by metabolic autoregulatory mechanisms in response to pressure-induced augmentations in cardiac workload. The authors conclude that the myocardium is not at risk when phenylephrine is used to treat hypotension in patients with adequate cardiac function and coronary vasodilator reserve.