It is a common opinion that nitrate therapy may have a harmful effect on cardiac output in patients with congestive heart failure when left ventricular filling presssure is markedly reduced. In this study, we evaluated, using hemodynamic monitoring with Swan-Ganz catheterization, the effects on cardiac output and filling pressures of high-dose intravenous nitroglycerin in 8 patients with dilated cardiomyopathy and severe heart failure. At maximal doses of nitroglycerin utilized (350 ± 220 µg/m, range 100-800), a significant reduction in right atrial pressure (from 4 + 3.5 to -1 + 4 mm Hg, p < 0.001) and pulmonary capillary wedge pressure (from 16 ± 5 to 7 ± 3 mm Hg, p < 0.001) was observed. Furthermore, we found neither a significant reduction in systemic vascular resistances (from 1,500 ± 329 to 1,320 ± 330 dynes/s/cm-<sup>5</sup>) nor changes in heart rate or blood pressure. Finally, stroke volume and cardiac index increased slightly although not significantly (from 62 ± 18 to 70 ± 16 ml and from 2.3 ± 0.45 to 2.65 ± 0.41/m/m<sup>2</sup>). The preservation of stroke volume despite a marked reduction in left ventricular filling pressure can be explained by a reduction in pericardial constraint and of mitral regurgitation induced by nitroglycerin. The clinical implications of these hemodynamic results are discussed with emphasis on the short- and long-term use of nitrates in congestive heart failure.