In a randomized, double-blind study, 24 sea-level residents drove to 3,800-m altitude in 1 day, and then slept the first night in either ambient air or 24% oxygen, and the second night in the treatment that they did not receive on the first night. Oxygen enrichment, compared with ambient air, resulted in significantly fewer apneas, and significantly less time spent in periodic breathing during the night. The increase in SaO2 between evening and morning was significantly higher after sleeping in the oxygen-enriched atmosphere, compared with ambient air. However, this significant improvement in SaO2 did not persist into mid-day. The overnight treatment did not alter the ventilatory response to hypoxia or to carbon dioxide as measured the following morning. The results suggest that the elevation in SaO2 following overnight oxygen enrichment is probably not due to a change in the control of ventilation, but possibly to differences in subclinical lung pathology.