Nitroglycerin and nifedipine have been suggested as useful agents in the therapy of congestive heart failure. Because of the rapid action and feasability for sublingual administration of both drugs, their comparative hemodynamic and neurohumoral effects were studied in 12 patients with congestive heart failure. After sublingual nitroglycerin, there was a significant decrease in mean arterial pressure (96 +/- 17 to 90 +/- 15 mm Hg, p less than 0.01), left ventricular (LV) filling pressure (30 +/- 12 to 22 +/- 10 mm Hg, p less than 0.01), right atrial pressure (15 +/- 6 to 10 +/- 5 mm Hg, p less than 0.01) and systemic vascular resistance (21.5 +/- 7.7 to 19.3 +/- 6.2 units, p less than 0.05) and an increase in cardiac index (2.2 +/- 0.6 to 2.4 +/- 0.7 liters/min/m2, p less than 0.05) and LV stroke work index (20.4 +/- 7.0 to 24.5 +/- 8.6 gm-m/m2, p less than 0.01). After sublingual nifedipine, there was also a significant decrease in mean arterial pressure (96 +/- 16 to 89 +/- 14 mm Hg, p less than 0.01) and systemic vascular resistance (22.1 +/- 7.1 to 18.0 +/- 6.1 units, p less than 0.01) and an increase in cardiac index (2.1 +/- 0.6 to 2.4 +/- 0.6 liters/min/m2, p less than 0.01); in contrast to nitroglycerin, this was unaccompanied by significant changes in right- or left-sided filling pressures or LV stroke work index.(ABSTRACT TRUNCATED AT 250 WORDS)