Prediction of the development of acute mountain sickness (AMS) in individuals going to high altitudes is still a matter of debate. Whereas some studies found that subjects with a blunted hypoxic ventilatory response (HVR) are predisposed to AMS, others did not. However, the HVR has often been determined under very acute (5 to 10 min) isocapnic hypoxia without consideration of the subsequent hypoxic ventilatory decline (HVD), and the assessment of AMS susceptibility was based on a single altitude exposure. Therefore, the aim of the present study was to evaluate the relationship between the individual arterial oxygen saturation (Sa(O2)) after a 20- to 30-min exposure to poikilocapnic hypoxia and the AMS susceptibility based on repeated observations. A total of 150 healthy male and female mountaineers (ages: 42 +/- 13 yr), 63 of whom had known susceptibility to AMS and 87 of whom never suffered from AMS, were exposed to various degrees of normobaric and hypobaric hypoxia. Sa(O2) values were taken by finger pulseoximetry after 20 to 30 min of hypoxic exposure. Sa(O2) values after 20 to 30 min of hypoxia were on average 4.9% lower in subjects susceptible to AMS than in those who were not. Logistic regression analysis revealed altitude-dependent Sa(O2) values to be predictive for AMS susceptibility. Based on the derived model, AMS susceptibility was correctly predicted in 86% of the selected individuals exposed to short-term hypoxia. In conclusion, Sa(O2) values after 20 to 30 min of exposure to normobaric or hypobaric hypoxia represent a useful tool to detect subjects highly susceptible to AMS.