In 12 patients with severe congestive heart failure (CHF) due to ischemic heart disease or nonischemic cardiomyopathy the hemodynamic response to intravenous infusion of sodium nitroprusside (N) was compared to that of dobutamine (D) 10 μ/kg/min. D and N produced comparable increases in cardiac output (CO) (2.8 to 5.8 L/min and 2.9 to 5.0 L/min, respectively), but, compared to N, D caused a higher arterial pressure (99.3 vs 86.2 mm Hg, P <0.01) and heart rate (102.5 vs 95.3, P <0.05) and less reduction in pulmonary wedge pressure (PWP) (28.9 to 20.2 mm Hg vs 29.1 to 16.6 mm Hg, P <0.05). In five additional patients N and D were studied separately and then were infused together. The combination resulted in a higher CO, lower PWP and greater reduction in systemic and pulmonary vascular resistances than either drug alone. Brachial arterial infusion of nitroprusside produced prominent forearm vasodilation in a dose less than 10% of the systemic dose, whereas vasodilation with dobutamine was only modest even when 50% of the systemic dose was infused. Therefore, potent inotropic and vasodilator drugs produce similar and additive augmentation of left ventricular performance in heart failure. Reduction in vascular resistance with dobutamine probably is largely of reflex origin, but the vasodilation itself may be an important determinant of the rise in cardiac output.