This double-blind cross-over study evaluates in 12 male volunteers the time course of nitroglycerin concentration in plasma with use of the TTS-nitroglycerin, a controlled-release transdermal dosage form for nitroglycerin, and compares the bioavailability of nitroglycerin delivered from the transdermal system with that from three successive applications of 0.5 inch of 2% nitroglycerin ointment placed at 8 hr intervals over 10 cm2 of skin. The mean amounts of nitroglycerin available when subjects wore the TTS-nitroglycerin or received successive applications of ointment were 15.8 mg +/- 1.8 (SE) and 9.8 mg +/- 0.8, respectively. Mean plasma concentrations for both treatments ranged from 10-18 pg/ml-cm2. The normalized areas under the curves--353 and 410 pg/hr/ml-cm2, respectively--did not differ significantly. The ratio of clearance from the two dosage forms was 0.98 +/- 0.12. All subjects experienced mild-to-moderate side effects of nitrate therapy with both dosage forms and also decrease in blood pressure and increase in heart rate.