The antihypertensive effect of transdermal nitroglycerin was tested in 11 men with hypertension (mean age 60 years) whose diastolic blood pressure exceeded 90 mm Hg while receiving a diuretic and a beta-adrenergic blocker. In a double-blind, randomized crossover trial the subjects received weekly increments of placebo or nitroglycerin (5, 10, 20, and 30 cm2) for 4 weeks each. The final dose of nitroglycerin was 22.5 cm2 (mean). During week 4 of nitroglycerin dosing, sitting and standing systolic blood pressures were reduced (P less than 0.05). Diastolic blood pressures and heart rates did not change during the study. In the five subjects with systolic hypertension (greater than or equal to 150 mm Hg), the mean reduction in systolic blood pressure was 24 mm Hg (P less than 0.01). Further studies are needed to determine if transdermal nitroglycerin has a role in the treatment of systolic hypertension.