Atrial natriuretic peptide (ANP) is recognized as an "endogenous vasodilator". The purpose of this study was to determine the effects of a clinical therapeutic dose of synthetic alpha-human ANP on the coronary circulation in 15 subjects with normal coronary arteries and normal ventricular function. The epicardial coronary arterial diameter was measured by selective coronary arteriography. Coronary blood flow was estimated from the arterial cross-sectional area and the flow velocity determined using an subselective intracoronary Doppler catheter. ANP, 0.03 micrograms/min/kg given intravenously over 15 minutes, caused a dilation of the large epicardial coronary artery (n = 8): the diameter of the proximal left anterior descending artery dilated from 2.6 +/- 0.4 to 3.1 +/- 0.5 mm (p less than 0.01). Mean arterial pressure decreased from 89 +/- 5 to 83 +/- 5 mmHg (p less than 0.01); heart rate did not change during ANP infusion. Estimated coronary blood flow significantly increased (n = 6, p less than 0.01), and thus the coronary vascular resistance decreased after ANP infusion, suggesting an ANP-induced dilation of resistance vessels. The present study demonstrates that in human subjects a clinical dose of ANP by intravenous infusion dilates both the large epicardial and small resistance coronary vessels. These results suggest a potentially beneficial role for ANP in reducing the severity of myocardial ischemia in patients with ischemic heart disease.