The efficacy of nitroglycerin ointment was determined by treadmill exercise testing through a randomized, double-blind crossover trial with placebo in 22 patients with chronic stable exertional angina. On different days, 3 cm of nitroglycerin ointment (NGO, 18 mg) and placebo ointment were applied over the epigastric region, followed by the exercise test 1 hour later. The maximal exercise time was 459 +/- 124 seconds after application of placebo and 510 +/- 113 seconds after application of NGO, and the exercise time to 1 mm of ST-segment depression was significantly extended to 297 +/- 110 seconds after placebo and 366 +/- 134 seconds after NGO (p less than 0.01, p less than 0.001, respectively). ST-segment depression at the endpoint of exercise was significantly reduced from 2.4 +/- 1.2 mm to 1.5 +/- 0.7 mm after application of NGO (p less than 0.01). There was no difference in rate-pressure product at the endpoint of exercise between placebo and NGO. Adverse reactions were elicited in 5 of 22 patients. The results of this present study suggest that NGO is effective in the treatment of exertional angina.