Hypoxia inhibits activity and expression of transport proteins of cultured lung alveolar epithelial cells. Here we tested whether hypoxia at high altitude affected the expression of ion transport proteins in tissues obtained from controls and mountaineers with high-altitude pulmonary edema (HAPE) at the Capanna Margherita (4,559 m). Expression was determined by RT-PCR and Western blots from brush biopsies of bronchial epithelium and from leukocytes obtained before and during the stay at high altitude. At low altitude, amounts of mRNAs were not different between control and HAPE-susceptible subjects. At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly (-60%) in HAPE-susceptible subjects. There was no change in Na channel mRNAs at high altitude in controls and HAPE. No statistically significant correlation was found between the expression of Na transporters and PO2 and O2 saturation. In leukocytes, 28S-rRNA and Na-K-ATPase decreased at altitude in control and HAPE-susceptible subjects, but no significant change in Na-K-ATPase protein was found. Hypoxia-inducible factor-1alpha mRNA and GAPDH mRNA tended to increase in leukocytes obtained from HAPE-susceptible subjects at high altitude but did not change in controls. These results show that hypoxia induces differences in mRNA expression of ion transport-related proteins between HAPE-susceptible and control subjects but that these changes may not necessarily predict differences in protein concentration or activity. It is therefore unclear whether these differences are related to the pathophysiology of HAPE.