Objective: This study was intended to demonstrate a biologically important association between acute mountain sickness (AMS) and sleep disordered breathing. Methodology: A total of 14 subjects (eight males, six females aged 36 10 years) were studied at six different altitudes from sea level to 5050 m over 12 days on a trekking route in the Nepal Himalaya. AMS was quantified by Lake Louise (LL) score. At each altitude, sleep was studied by 13 channel polysomnography (PSG). Resting arterial blood gases (ABG) and exercise SaO(2) were measured. Ventilatory responses (VR) were measured at sea level. Individual data were analysed for association at several altitudes and mean data were analysed for association over all altitudes. Results: ABG showed partial acclimatization. For the mean data, there were strong positive correlations between LL score and altitude, and periodic breathing, as expected. Strong negative correlations existed between LL score and PaO2, PaCO2, sleep SaO(2) and exercise SaO(2), but there was no correlation with sea level VR. There were equally tight correlations between LLs/PaO2 and LL score/sleep SaO(2). The individual data showed no significant correlations with LL score at any altitude, probably reflecting the non-steady state nature of the experiment. In addition, mean SaO(2) during sleep was similar to minimum exercise SaO(2) at each attitude and minimum sleep SaO(2) was lower, suggesting that the hypoxic insult during sleep was equivalent to or greater than walking at high altitude. Conclusions: It is concluded that desaturation during sleep has a biologically important association with AMS, and it is speculated that under similar conditions (trekking) it is an important cause of AMS.