Hypoxia inhibits activity and expression of ion transport proteins of cultured lung alveolar epithelial cells. Here we tested, whether in vivo hypoxia at high altitude (4,559 m) also inhibits lung ion transport. Transepithelial nasal potentials (NP) were determined as a surrogate measure of lung ion transport activity before and during the stay at altitude. In normoxia, total NP was approximately 20% higher in control subjects than in susceptibles to high-altitude pulmonary edema, but there was no difference between groups in amiloride-inhibitable NPs. At high altitude total NP increased 250% in both groups, whereas amiloride-sensitive NP decreased in control subjects only (-80%), and the chloride ion (Cl-)-sensitive portion of NP almost doubled. Because many mountaineers suffer from nasal dryness at high altitude, a control study was performed in normobaric hypoxia (12% oxygen, 6 hours) at a controlled humidity of 50%. In this study, no change in total NP or its amiloride- and Cl-sensitive portions was observed. The increased Cl- secretion at high altitude but no such change in normobaric hypoxia suggests that nasal dryness may stimulate local active Cl- and fluid secretion in the upper respiratory tract. It is therefore uncertain whether similar changes also occur at the alveolar epithelium.