Atrial natriuretic peptide has been reported to cause vasoconstriction, vasodilation or no change of coronary vascular resistance in isolated perfused hearts or in open chest animal models. Because general anesthesia and acute surgical trauma may perturb baseline coronary hemodynamics and alter responses to experimental interventions, this study examined the effects of human atrial natriuretic peptide (arginine-102-tyrosine-126) and rat atriopeptin II (serine-103-arginine-125) on the coronary circulation of unsedated, awake dugs. Studies were performed in 12 chronically instrumented animals in which a surgically implanted electromagnetic flow probe and intracoronary catheter allowed measurement of left circumflex coronary blood flow during intraarterial administration of the atrial natriuretic peptides. Bolus doses of both human atrial natriuretic peptide and rat atriopeptin II produced dose-dependent coronary vasodilation; the threshold for coronary vasodilation was 0.2 μg/kg body weight for both agents. Coronary vasodilation produced by human atrial natriuretic peptide was not antagonized by adenosine receptor blockade or by cyclooxygenase inhibition with indomethacin. Thus, atrial natriuretic peptides produced dose-dependent coronary vasodilation in intact awake dogs that was not dependent on adenosine-mediated or prostaglandin-mediated mechanisms.