Fifty-six patients with angina pectoris on effort participated in a 28-day study comparing a transdermal nitroglycerin system (TNS) against placebo. The protocol was based on a regular double-blind multi-crossover pattern. The variables recorded included daily sublingual nitroglycerin requirement, daily anginal attack frequency, and a subjective patient evaluation of each day on a visual analog scale. TNS dosage ranged from 10 cm2 (5 mg per 24 h) to 60 cm2 (30 mg per 24 h) based on the patient's dosage prior to commencement of the study. All other medication was continued unchanged. The results demonstrate improvement on active therapy in the patient group using greater than or equal to 20 cm2 TNS whereas no significant improvement in patients using 10 cm2 TNS was seen. In the higher dose group, the mean number of daily anginal attacks was 2.5 on placebo and 1.4 on active therapy (P less than 0.0001). Corresponding mean daily sublingual nitroglycerin requirement was 3.6 on placebo and 2.3 on active therapy (P less than 0.0001). Although TNS therapy was associated with significant improvement in the group using the higher dosage, the results suggest the development of tolerance on active therapy. The possibility of rebound effect and the absence of demonstrable efficacy in the low dose group require further investigation.