Residence at high altitude modifies thremoregulatory responses to cold stress upon return to lower altitude. These changes are difficult to explain since several stresses related to high altitude may interact, including hypoxia, cold, solar radiation, and physical exertion. We hypothesized that adaptation to hypoxia without cold exposure would produce at least part of the observed changes.Five men underwent acclimation to intermittent hypoxia (AIH) in a hypobaric chamber (8 h daily for 4 d, and 6 h on the last day, 4500 to 6000 m) at 24 degrees C. Cold stress responses were tested during a whole-body standard cold air test (1 degrees C, 2 h at rest at sea level) both before and after AIH.Increased reticulocyte counts and percentages confirmed acclimation to hypoxia after AIH. Changes in thermoregulation during the cold test included lower mean skin temperature after 60-80 min (18.8 +/- 0.7 degrees C vs. 19.4 +/- 0.7 degrees C); higher mean metabolic heat production (127 +/- 8 W x m(-2) vs. 118 +/- 6 W x m(-2)); and lower heat debt (7.7 +/- 1.3 kJ x kg(-1) vs. 10.3 +/- 1.2 kJ x kg(-1)), without significant change in rectal temperature. Time to onset for continuous shivering decreased after AIH (12 +/- 5 min vs. 21 +/- 6.3 min), and shivering activity occurred at higher mean skin but not rectal temperatures.AIH in comfortable ambient temperature leads to a normothermic-insulative-metabolic general cold adaptation. We conclude that AIH modifies the thermoregulatory responses to cold at sea level without cold exposure leading to a cross-adaptation.