Context: Sleep is disturbed at high altitudes. Low Po 2 levels at high altitude cause hyperventilation, which results in secondary hypocapnia (low Paco 2 levels). Thus, although sleep disruption at high altitudes is generally assumed to be caused by hypoxia, it may instead be the result of hypocapnia. Objective: To determine whether hypocapnia disrupts sleep. Methods: Four cats were studied for a total of 345 hours of sleep recordings. Two methods were used to test this idea. First we studied their sleep when the cats breathed oxygen concentrations (15% and 10%) equivalent to those at approximately 12,000 feet and 21,000 feet. Then we studied their sleep again in response to the same hypoxic stimuli but with CO 2 added to the inspirate to maintain normal CO 2 levels. Second, we used mechanical hyperventilation to vary the levels of CO 2 while maintaining normal O 2 levels. Results: Hypoxia (10% O 2 ) decreased the amount of rapid eye movement sleep to about 20% of normal, and adding back CO 2 restored rapid eye movement sleep to approximately 70% of normal. Periodic breathing and apneas were not observed during hypoxia in sleep. When mechanical hyperventilation lowered the CO 2 to 85%, 75%, and 65% of normal, rapid eye movement sleep decreased progressively from a control level of 17% of total recording time to 12%, 7%, and 4%, respectively. Conclusion: We conclude that hypocapnia rather than hypoxia may account for most of the sleep disturbance at high altitudes.