The present study was designed to investigate pharmacological vasodilation in patients with chronic obstructive pulmonary disease (COPD). This may have long-term therapeutic implications. Sublingual nitroglycerin (GTN) was administered to 16 patients with COPD and no evidence of organic heart disease (except one patient) in an attempt to determine severity of the decrease in arterial oxygenation. Gas exchange and hemodynamic studies were performed before and after GTN. Alverolar-arterial O2 tension gradient increased 5 mm Hg, arterial PO2 decreased 2 mm Hg, and cardiac output decreased from 4.36 to 3.85 liters/min. There was a decrease in pulmonary artery pressures, but pulmonary vascular resistance did not change. Total O2 transport (the product of cardiac output and arterial O2 content) decreased, due mainly to a decrease in cardiac output. From these studies we conclude that GTN significantly decreases O2 transport in patients with COPD and normal left ventricular function; this decrease is due mainly to a reduction in cardiac output. Impairment of gas exchange is slight. Based on these considerations pharmacological vasodilation with nitroglycerine in COPD is probably not warranted.