OBJECTIVE: To evaluate the influence of alcohol on acute adaptation to mild hypoxia at moderate altitude. DESIGN: Randomized, double-blind, placebo-controlled crossover trial. SETTING: University clinic and mountaineering resort at altitudes of 171 m and 3000 m, respectively, in the Austrian Alps. PARTICIPANTS: 10 healthy male alpinists, 22 to 24 years of age. INTERVENTION: Single dose of 50 g of alcohol or placebo at altitudes of 171 m and 3000 m. MAIN OUTCOME MEASURES: Arterial oxygen pressure (Pao2) and arterial carbon dioxide pressure (Paco2) before and 1 hour after consumption of alcohol or placebo. RESULTS: At an altitude of 171 m, 50 g of alcohol caused no statistical change in Pao2 and Paco2 (median Pao2, 91.5 compared with 90.5 mm Hg [P = 0.89]; median Paco2, 37.5 compared with 36.0 mm Hg [P = 0.41]). At an altitude of 3000 m, the median Pao2 decreased from 69.0 to 64.0 mm Hg, a median decrease in the paired difference of 4.0 mm Hg (95.1% CI, 1.5 to 6.5 mm Hg; P < 0.01), and the median Paco2 increased from 32.5 to 34.0 mm Hg, a median increase in the paired difference of 3.0 mm Hg (95.1% CI, 2.0 to 4.0 mm Hg; P < 0.01) 1 hour after drinking 50 g of alcohol. Placebo did not influence Pao2 or Paco2 at either altitude. CONCLUSION: Alcohol inhibits the initial stages of adequate acute ventilatory adaptation to mild hypoxia at moderate altitude. Caution in the use of alcoholic beverages at moderate altitude is therefore necessary.