To assess the effects of atrial natriuretic factor (ANF) on cardiac function, synthetic human ANF was infused directly into the left main coronary artery of eight patients with congestive heart failure (CHF) and six subjects with normal left ventricular (LV) function (controls) who underwent cardiac catheterization. ANF infusion at the incremental rates of 60, 125, 400, and 800 ng/min induced a dose-related increase in plasma ANF concentrations in the coronary sinus, from 1,223 +/- 590 to 3,923 +/- 1,123 pg/ml in patients with CHF (p < 0.01) and from 1,041 +/- 605 to 2,710 +/- 1,741 pg/ml in controls (p < 0.01). Peripheral plasma ANF concentrations (femoral artery) increased from 538 +/- 278 to 752 +/- 262 pg/ml (p < 0.01) in patients with CHF and from 193 +/- 63 to 401 +/- 147 pg/ml (p < 0.01) in controls. The increase in peripheral or coronary sinus plasma ANF concentrations did not differ between patients with CHF and controls. At the three lowest ANF infusion rates, cardiac index (CI), systemic vascular resistance (Svr), and LV contractility assessed by peak positive dP/dt remained unchanged both in patients with CHF and in controls. At the highest ANF infusion rate, CI increased from 2.18 +/- 0.53 to 2.54 +/- 0.49 L/min/m2 (p < 0.01) and SVR decreased from 14.6 +/- 3.6 to 12.8 +/- 4.5 mm Hg.min/L (p < 0.01) in patients with CHF. There was no associated change in heart rate (HR), mean arterial blood pressure (MAP), cardiac filling pressures, or peak positive dP/dt. Coronary resistance decreased slightly although no change occurred in coronary blood flow. In controls, hemodynamic parmeters remained unchanged at any ANF infusion rate. These data show that direct infusion of ANF into the left coronary artery does not affect LV contractility in subjects with normal or altered LV function. Improvement of LV function in patients with CHF resulted mainly from the vasodilating activity of ANF.