Osmoregulation was studied in 13 mountaineers who had experienced long-term exposure to high altitude on Mt Everest. Serum osmolality rose from 290 +/- 1 mOsm/kg to 295 +/- 2 mOsm/kg at 5,400 m and finally to 302 +/- 4 mOsm/kg at 6,300 m after a mean of 26.5 days above 5,400 m. Despite this degree of osmoconcentration, plasma arginine-vasopressin concentration remained unchanged: 1.1 +/-0.1 microU/mL at sea level, 0.8 +/- 0.1 microU/mL at 5,400 m, and 0.9 +/- 0.1 microU/mL at 6,300 m. Urinary vasopressin excretion was also similar at all three altitudes. We conclude that prolonged exposure to high altitude may result in persistent impairment of osmoregulation, caused in part by an inappropriate arginine-vasopressin response to hyperosmolality.