OBJECTIVE: We study the effect of short half-life hypnotics (zaleplon or zolpidem against placebo) on altitude tolerance in 12 nonacclimated male soldiers (age, 22.1 +/- 0.8 years; height, 177.8 +/- 1.7 cm; weight, 69.8 +/- 1.7 kg). METHODS: Soldiers were trained to practice mountaineering at high altitude (2,533-4,810 meters) during 3 periods (one per medication tested) of 4 days (D1-D4). In each period the nights were spent in a hut (3,613 m). Administration of hypnotics or placebo was then implemented at 9:45 p.m. Nocturnal arterial oxygen saturation (SaO2) and heart rate variability (HRV) were monitored. At 5:00 a.m. and 9:00 p.m. physical fitness was assessed using acute mountain sickness (AMS) score. At 5:00 p.m., a posteffort stand test was carried out to evaluate the orthoparasympathetic imbalance with fatigue. RESULTS: Nocturnal SaO2 correlated negatively with morning AMS scores (R = -0.820, p < 0.02) and HRV analysis favored the sympathetic modulation. Posteffort stand tests revealed that sympathetic modulation attenuated from D2 to D3 in treated groups. CONCLUSION: The present study provides evidence that zolpidem or zaleplon improves sleep and subsequent physical fitness at altitude.