Acute hemodynamic and hormonal responses to a single dose of indoramin, an α1-antagonist, were evaluated in 11 subjects with severe chronic congestive heart failure. A hemodynamic effect began within 1 hr of indoramin and persisted during the 6 hr of hemodynamic monitoring. Decreased right and left ventricular filling pressures were associated with increased stroke index and decreased pulmonary and systemic vascular resistances. Heart rate did not increase despite a fall in systemic arterial pressure. Forearm blood flow, forearm venous capacitance, and plasma norepinephrine levels were unchanged, whereas plasma renin activity rose from 12.7 ± 17.4 to 16.6 ± 20.4 ng/ml/hr. The only side effect was drowsiness in five of the 11 subjects. Our data demonstrate the acute effectiveness of indoramin in reducing ventricular preload and systemic vascular resistance in heart failure.