The present study was concerned with the pathogenesis of pulmonary arterialhypertension in 21 patients with the pulmonary complications of cystic fibrosis. Respiratory function tests failed to distinguish between patients with normal pulmonary arterial pressure and those with pulmonary hypertension. On the other hand, the pulmonary arterial pressure was directly related to the degree of hypoxia. Relief of hypoxia, either acutely by breathing high-oxygen mixtures, or chronically by the treatment of respiratory infection and bronchial drainage, returned pulmonary arterial pressure toward, or to, normal. These physiologic observations imply a predominant role for hypoxia in the pathogenesis of pulmonary hypertension in cystic fibrosis, and indicate its potential reversibility in this disease.