The authors' previous studies have demonstrated that IV administration of atrial natriuretic peptide (ANP) produces a dose dependent decrease in pulmonary arterial pressure in rats adapted to chronic hypoxia. To examine the effects of ANP on chronic hypoxic pulmonary hypertension in man, α-human ANP (200 μg) was infused (20 μg/min x 10 min) into the right atrium via a Swan-Ganz catheter in four patients with pulmonary hypertension of high altitude. Following the infusion, pulmonary arterial pressure fell gradually and remained depressed for 1 hour. Peak reductions in pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (MPAP) were 23% and 30%, respectively. Systemic arterial pressure, cardiac output and cardiac index also tended to decrease, but these changes did not reach statistical significance. The data suggest that ANP is useful in the treatment of chronic hypoxic pulmonary hypertension in man.