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 (β-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 < 0.05). Diastolic blood pressures and heart rates did not change during the study. In the five subjects with systolic hypertension (%150 mm Hg), the mean reduction in systolic blood pressure was 24 mm Hg (P < 0.01). Further studies are needed to determine if transdermal nitroglycerin has a role in the treatment of systolic hypertension. (Clin Pharmacol Ther 1986;40:42-5.).