To determine the safety and efficacy of single oral doses of quinapril in the treatment of congestive heart failure (CHF), an open-label, hemodynamic trial was conducted in 11 patients with severe CHF [New York Heart Association (NYHA) class III or IV] in whom previous or current therapy with diuretics and digitalis had been inadequate. After participating in this single-dose trial (acute phase), all 11 patients were entered into a 16-week, multiple-dose investigation (chronic phase). In the acute phase of the study, single oral doses of quinapril (2.5, 5, and 10 mg/day) achieved beneficial hemodynamic changes within 1 h after the onset of therapy. Maximal improvements in key hemodynamic variables (i.e., pulmonary capillary wedge pressure, mean arterial blood pressure, cardiac output, and total systemic vascular resistance) were observed within 4 h after dosing. The hemodynamic changes after 16 weeks of chronic quinapril therapy (5, 10, 15, and 30 mg/day) were equivalent or superior to those observed after acute therapy, indicating that quinapril produces a sustained hemodynamic benefit after chronic oral dosing. Quinapril was shown to be safe and effective in the treatment of patients with severe CHF. © 1990 Raven Press, Ltd., New York.