Atrial natriuretic peptide (hANP 4–28) was infused for 1 h (0.3 μg/kg/min) in 11 normal awake dogs and seven awake dogs with chronic left ventricular dysfunction, induced 16 weeks earlier by repetitive DC shock. The responses were similar in the two groups and included decreases in arterial pressure (107–99 mm Hg), heart rate (83–72 beats/min), and cardiac output (3.6–2.8 L/min), without changes in right or left ventricular filling pressures. Systemic vascular resistance (SVR) tended to rise during the infusion and was significantly increased (2,847–3,442 dyn s cm−5, p < .05) during the postinfusion recovery period. Regional blood flows (microspheres) during infusion revealed a decrease in skin and splanchnic flow. Despite the apparent vasoconstrictor effect, plasma norepinephrine (PNE), renin activity (PRA), and arginine vasopressin (AVP) levels all fell during ANP infusion. These data suggest that ANP exerts a cardioinhibitory effect, possibly similar to that of arginine vasopressin (AVP), and that the net systemic vasoconstrictor effect of ANP in these dogs is mediated by a complex interrelationship between direct vascular effects, neurohormonal inhibition, and central reflex activation.