We compared the acute hemodynamic effects of captopril and nitrates in 11 patients with severe congestive heart failure and Grade IV cardiac disability. Pressures were measured using a Swan-Ganz catheter system; cardiac output and stroke index were measured by thermodilution, and left-ventricular (LV) volumes and ejection fraction were calculated simultaneously with the hemodynamic measurements from radionuclide ventriculography. Measurements were made in each of four treatment states: control, sublingual isosorbide dinitrate (ISDN) (5 and 15 mg), oral captopril (50 to 200 mg daily) and during combined therapy with captopril and ISDN. Captopril produced a fall in mean arterial pressure (P less than 0.01) from 81 +/- 14 to 72 +/- 13 mm Hg, and a rise in stroke index from 30 +/- 5 to 35 +/- 91/min per m2 (P less than 0.05), while LV ejection fraction increased from 18 +/- 5 to 21 +/- 7% (P less than 0.05). ISDN reduced mean arterial, pulmonary arterial, right-atrial and wedge pressure. The combination of captopril and ISDN produced a greater fall in mean arterial pressure, a further rise in ejection fraction to 22 +/- 8% (P less than 0.05), a fall in systemic (P less than 0.05) and pulmonary vascular resistance (P less than 0.01) and a rise in cardiac (P less than 0.01) and stroke work index (P less than 0.01), while the beneficial effects of ISDN on right-atrial, pulmonary arterial and wedge pressure were again achieved. LV contractility, assessed from end-systolic stress-shortening relations, was essentially unaltered or decreased very slightly. The study showed that combined therapy with captopril and nitrates produced acute hemodynamic benefits superior to those achieved by treatment with captopril or nitrates alone.