High altitude pulmonary edema (HAPE) is characterized by marked pulmonary hypertension. Treatment of 6 subjects suffering from radiographically documented HAPE with the calcium channel blocker nifedipine, lowered pulmonary artery pressure and resulted in clinical improvement, better oxygenation, reduction of alveolar-arterial oxygen gradient and a progressive clearing of alveolar edema on chest x-ray. This amelioration occurred despite continued exercise at an altitude above 4000 m and without supplementary oxygen. Prophylactic application of nifedipine slow release preparation, 20 mg every 8 hours, prevented HAPE in 9 out of 10 subjects with a history of radiographically documented HAPE upon rapid ascent and subsequent stay to an altitude of 4559 m. Seven of 11 comparable subjects who received placebo developed pulmonary edema at 4559 m. As compared with the subjects who received placebo, those who received nifedipine had a significantly lower mean systolic pulmonary artery pressure, alveolar-arterial pressure gradient of oxygen and symptom score of acute mountain sickness at 4559 m. Thus nifedipine offers a potential emergency treatment of HAPE when descent or evacuation is impossible and oxygen is not available. Prophylactic administration of nifedipine prevents HAPE in susceptible subjects. High pulmonary artery pressure has an important role in the pathogenesis of HAPE.