The construction of the Qinghai-Tibet railroad provided a unique opportunity to study the relation between intermittent altitude exposure and acute mountain sickness (AMS). For 5 yr, workers spent 7-month periods at altitude interspaced with 5-month periods at sea level; the incidence, severity, and risk factors of AMS were prospectively investigated. Six hundred lowlanders commuted for 5 yr between near sea level and approximately 4500 m and were compared to 600 other lowland workers, recruited each year upon their first ascent to high altitude as newcomers, and to 200 Tibetan workers native to approximately 4500 m. AMS was assessed with the Lake Louise Scoring System. The incidence and severity of AMS in commuters were lower upon each subsequent exposure, whereas they remained similar in newcomers each year. AMS susceptibility was thus lowered by repeated exposure to altitude. Repeated exposure increased resting Sao(2) and decreased resting heart rate. Tibetans had no AMS, higher Sao(2), and lower heart rates. In conclusion, repetitive 7-month exposures increasingly protect lowlanders against AMS, even when interspaced with 5-month periods spent at low altitude, but do not allow attaining the level of adaptation of altitude natives.