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Although the recently introduced patches containing nitroglycerin for transdermal absorption have already gained widespread use in the treatment of angina pectoris, convincing evidence as to their efficacy has yet to accumulate. Major unresolved questions concern the patch area (dose) necessary to achieve an antianginal effect, whether such an effect, once achieved, will be sustained throughout the day, and whether tolerance during long-term use will totally or partially neutralize any initial therapeutic effect. The present investigation was undertaken to address these unresolved issues by studying a small number of patients with classic angina pectoris and demonstrated nitrate responsiveness. We were governed at the outset by several basic premises: first, that the effectiveness of nitrates is very dose dependent, with considerable individual variation; second, that duration of exercise to angina in a supervised test is the best end-point for dose titration; and third, that in order to obtain a patch dose which might be effective during long-term use, titration should be carried out in patients already receiving long-term nitrate therapy, who, although probably partially nitrate tolerant, are still nitrate responsive.