Nitroglycerin ointment (12.5 to 50 mg) was administered in randomized fashion to three skin sites, arm, chest, or thigh, to compare the hemodynamic effects and bioavailability in nine patients with severe congestive heart failure. Hemodynamic parameters and arterial nitroglycerin concentrations were measured frequently for 12 hours after each application and for 90 minutes after removal of the ointment. During the study, left ventricular filling pressures decreased from control values of 25.0 +/- 8.6 mm Hg (arm), 25.7 +/- 10.9 mm Hg (chest), and 23.7 +/- 8.4 mm Hg (thigh) to 20.4 +/- 8.6 mm Hg, 20.4 +/- 8.5 mm Hg, and 20.0 +/- 7.5 mm Hg; p less than 0.05, less than 0.01, and difference not significant respectively. Peak nitroglycerin concentrations were 5.1 +/- 4.3 ng/ml (arm), 6.2 +/- 6.0 ng/ml (chest), and 4.1 +/- 6.3 ng/ml (thigh). No significant difference was observed in mean arterial pressure, left ventricular filling pressure, right atrial pressure, or nitroglycerin concentration among the sites. These data show that nitroglycerin ointment has similar bioavailability on the arm, chest, or thigh and therefore can be used interchangeably on these skin sites.