The antianginal efficacy of a transdermal therapeutic delivery system for nitroglycerin (TNG) was compared with that of placebo in a double-blind crossover study. Twenty-five patients with stable angina pectoris were evaluated. The transdermal system delivered 5 mg of nitroglycerin over a 24-hour period and was applied once every 48 hours. Treadmill exercise testing (Bruce protocol) was done 48 hours after the patch was applied in the first phase of the crossover and at the conclusion of the second phase of the crossover, 48 hours after the final dose of the second treatment. Exercise performance was significantly improved (P less than 0.05, analysis of covariance) with TNG as compared with placebo, as were frequency of episodes of angina and nitroglycerin consumption (P less than 0.05, analysis of variance). The incidence of mild-to-moderate headache in patients was greater during treatment with TNG (20%) than during placebo treatment (6.7%). Four cases of mild transient dermatitis and occasional reports of dizziness, lightheadedness, and nausea were noted.