The ability of newer airliners to fly at higher altitudes has resulted in an increased altitude exposure to both airline crews and passengers. This increase in altitude exposure has the potential to place some individuals at risk for desaturation. Using pulse oximetry, the arterial oxygen saturation of 42 airline crew members was continuously monitored on 22 regularly scheduled commercial flights. Mean nadir arterial oxygen saturations fell from 97.0% preflight to 88.6% at cruising altitudes. Pulse oximetry results revealed large variations between individuals. Individual nadir saturations ranged from 93% to 80%. Modern aircraft flight may result in desaturations even among healthy aircrew. The effects on human performance remain unknown.