Therapy of pulmonary hypertension is limited by the low potency and adverse effects of current pulmonary vasodilators. The hemodynamic effects of nitroglycerin in human pulmonary hypertension are not known. We administered nitroglycerin to nine patients with chronic pulmonary hypertension. Nitroglycerin increased cardiac index 40% (p less than 0.01), increased stroke volume 40% (p less than 0.01), decreased pulmonary vascular resistance 40% (p less than 0.01), and decreased mean pulmonary artery pressure 15% (p less than 0.01). Pulmonary vascular resistance decreased more than 25% in eight of the nine patients. In four patients the effects of intravenous nitroglycerin were reproduced by topical nitroglycerin preparations; cardiac index increased 50%, stroke volume increased 48%, pulmonary vascular resistance decreased 43%, and mean pulmonary artery pressure decreased 19%. Five of six patients treated with long-acting nitrates had substantial improvement of their symptoms. We conclude that therapy with nitroglycerin can be effective in patients with severe pulmonary hypertension.