Nitrates have been used for long-term vasodilator therapy of left ventricular failure. Whereas left ventricular filling pressure (LVFP) consistently decreases, cardiac output does not always increase after nitrate administration, suggesting that preload reduction may be the predominant action of these agents in congestive heart failure. In 28 patients with chronic congestive heart failure due to cardlomyopathy, nitrate administration reduced mean systemic arterial pressure from 91.9 to 83.6 mm Hg, LVFP from 29.3 to 19.0 mm Hg and systemic vascular resistance from 33.2 to 24.0 U. Cardiac index increased from 1.70 to 2.09 liters/min/m2. All changes were significant (p < 0.001). The change in cardiac index after nitrate administration correlated positively with the control LVFP (r = 0.52) and inversely with the control cardiac index (r = 0.52). In six patients, nitrate effects were compared to those of preload reduction with the application of tourniquets and outflow resistance reduction with the administration of nitroprusside. All three interventions reduced LVFP comparably and significantly, tourniquets by 6.3 mm Hg, nitroprusside by 9.3 mm Hg and nitrates by 8.7 mm Hg. The cardiac index decreased 0.16 liters/min/m2 after tourniquets, but increased 0.50 liters/min/m2 during nitroprusside therapy and 0.21 liters/min/m2 after the administration of nitrates. The differences in cardiac index response between tourniquets and the two vasodilators were statistically significant, as was that between nitroprusside and nitrates. We conclude that the hemodynamic actions of nitrates in congestive heart failure are qualitatively similar to those of nitroprusside, but quantitatively less. Nitrates reduce outflow resistance as well as preload in congestive heart failure, and the magnitude of the former response is dependent upon the base line cardiac index and LVFP.