This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 AM application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p < 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p < 0.001). (After placebo patches: + 19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 PM, p < 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical.