There are few data to support the potential efficacy of combined vasodilator therapy for severe congestive heart failure. For documentation of the feasibility of such an approach, a short-term hemodynamic study utilizing captopril, an oral converting enzyme inhibitor, followed by the addition of nitroprusside infusion, was made of 11 patients with severe chronic congestive heart failure. Captopril alone resulted in reduction of mean arterial pressure (84 +/- 7 to 70 +/- 3 mm Hg), associated with increase of cardiac index and stroke index. There was also a significant reduction of systemic resistance and pulmonary wedge pressure. The initial hemodynamic response to captopril was correlated with initial plasma renin activity (all values at least p less than 0.05). The addition of nitroprusside to captopril resulted in further hemodynamic improvement. Reduction of mean arterial pressure, systemic vascular resistance, and pulmonary wedge pressure were all significant, as were increases of cardiac index and stroke index. The degree of hemodynamic improvement with this sequence of vasodilator therapy was linearly related to the reduction of mean arterial pressure. Therefore vasodilators with dissimilar mechanisms of action may have an additive effect. These data support the potential feasibility of combined, long-term oral vasodilator therapy in selected subgroups of patients with congestive heart failure.