Enalapril, a new oral angiotensin converting-enzyme inhibitor, was administered to nine patients with severe congestive heart failure. Short-term hemodynamic response was noted within 2 hr and persisted for up to 24 hr. At peak effect mean arterial pressure fell from 83.4 ± 10(SD) to 72.1 ± 16.2 mm Hg (p<.01), right atrial pressure from 13.6 ± 6.0 to 10.4 ± 7.5 mm Hg (p<.01), pulmonary arterial pressure from 38.9 ± 4.8 to 31.9 ± 4.8 mm Hg (p<.01), pulmonary capillary wedge pressure from 28.2 ± 3.5 to 22.1 ± 5.1 mm Hg (p<.01), and total pulmonary resistance from 875 ± 304 to 697 ± 291 dynes-sec-cm-5 (p<.05). Cardiac index was not changed, but there was a significant redistribution of regional blood flow with an increase of renal blood flow after enalapril. Plasma renin activity rose significantly from 6.2 to 28.6 ng/ml/hr, whereas plasma norepinephrine did not change after enalapril. Seven patients were treated with enalapril for 4 weeks. Five patients reported symptomatic improvement. Five of six patients tested had an increase in both exercise time (NS) and maximum oxygen consumption (NS). Repeat hemodynamic evaluation in six patients after long-term enalapril therapy showed a - persistent effect with significant reductions in right atrial pressure from 13.8 ± 7.2 to 7/1 ± 4.7 mm Hg and in mean arterial pressure from 82.5 ± 10.4 to 76.6 ± 5.3 mm Hg and a significant increase in cardiac index from 2.1 ± 0.5 to 2.5 ± 0.5 l/min/m2 (all p<.05). Long-term therapy was well tolerated, even by two patients who had developed toxic side effects to another converting-enzyme inhibitor, captopril. Enalapril is therefore a long-acting oral converting-enzyme inhibitor with an acute vasodilatory effect that appears to be well tolerated during long-term administration in patients with congestive hear failure.