In 42 patients with moderate-to-severe congestive heart failure (CHF), the acute hemodynamic and neurohumoral response to the converting enzyme inhibitors (CEIs) captopril (CPT) and teprotide were measured. Plasma renin activity (PRA) was elevated and correlated with control plasma norepinephrine (PNE) but not with any of the control hemodynamics. Acutely after CEIs, significant (p < 0.001) decreases in right atrial pressure, pulmonary artery pressure (PAP), capillary wedge pressure (PCWP), mean arterial pressure (MAP), total systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and heart rate (HR, p < 0.002), as well as an increase in cardiac index (p < 0.001), were observed. Control PRA correlated with the degree of hemodynamic change for PAP (r = -0.64), PCWP (r = -0.60), MAP (r = -0.66), SVR (r = -0.61), and PVR (r = -0.61). Long-term CPT therapy in 12 of these patients resulted in symptomatic improvement and a marked increase in exercise tolerance (7.4 to 10.4 minutes, p < 0.009). These data suggest that CEIs effect beneficial acute hemodynamic improvements in depressed left ventricular function, leading to substantial reduction in disabling symptomatology and augmentation of exercise capacity in patients with stable severe CHF. Thus, CPT appears to provide well-tolerated, effective long-term ambulatory vasodilator therapy for advanced cardiac dysfunction.