To determine if the addition of preload reduction with nitrates would potentiate the acute vasodilator actions of nifedipine, we titered intravenous nitroglycerin in seven patients with severe congestive heart failure after they received a single oral dose of nifedipine. The peak hemodynamic effect of nifedipine occurred at 30 minutes, with large reductions of systemic vascular resistance (1831 +/- 128 to 1132 +/- 154 dynes X sec X cm-5; p less than 0.001) and mean arterial pressure (87 +/- 7 to 71 +/- 7 mm Hg; p less than 0.01). This was associated with an increase of stroke volume index from 22 +/- 3 to 27 +/- 3 ml/m2 (p less than 0.01) but no significant changes in heart rate, right atrial pressure, or pulmonary wedge pressure. These hemodynamic changes were attenuated over a 2-hour observation period. At 2 hours, the addition of intravenous nitroglycerin resulted in large reductions in right atrial pressure (9 +/- 2 to 6 +/- 1; p less than 0.01) and pulmonary wedge pressure (23 +/- 2 to 17 +/- 2; p less than 0.001). This was associated with further increases in cardiac index (from 1.99 +/- .15 to 2.25 +/- .14 L/min/m2; p less than 0.001) and stroke volume index (26 +/- 3 to 29 +/- 3 ml/m2; p less than 0.01). Thus, the addition of nitroglycerin to nifedipine will optimize preload reduction and enhance the vasodilator action of nifedipine. Further controlled studies are necessary to determine the long-term hemodynamic effects and the clinical role of nifedipine and its combination with nitrates in patients with severe congestive heart failure.