Synthetic analogues of atrial natriuretic factor (ANF) have been developed for potential use as therapeutic agents in the treatment of congestive heart failure and hypertension. We studied the effects of 14 intravenous infusions of synthetic ANF (anaritide, human ANF 102-126) on coronary hemodynamics and myocardial energetics in six patients with heart failure. ANF infusion caused no change in coronary blood flow and a fall in coronary vascular resistance from 1.22 +/- 0.22 to 1.08 +/- 0.18 mm Hg-min/ml (p less than 0.05). Myocardial oxygen and lactate consumption were unchanged from baseline values. Mean arterial pressure fell from 91 +/- 4 to 78 +/- 3 mm Hg (p less than 0.01), right atrial pressure fell from 10 +/- 1 to 8 +/- 1 mm Hg (p less than 0.01), pulmonary capillary wedge pressure fell from 21 +/- 3 to 16 +/- 2 mm Hg (p less than 0.01), heart rate and cardiac index were unchanged, and systemic vascular resistance fell from 1346 +/- 130 to 1087 +/- 98 dyne-sec/cm5 (p less than 0.05). We conclude that infusion of ANF in hemodynamically effective doses in patients with heart failure decreases coronary vascular resistance with no change in coronary blood flow or myocardial oxygen or lactate metabolism.