Acute mountain sickness (AMS) can occur during climbs to high altitudes and may seriously disturb the behavioral and intellectual capacities of susceptible subjects. During a Himalayan expedition 32 mountaineers were examined with electroencephalography (EEG) and transcranial doppler sonography (TCD) to assess relative changes of middle cerebral artery velocity in relation to end-expiratory CO2 (EtCO2), peripheral saturation (SaO2), and symptoms of AMS. We tested the hypothesis that O2 desaturation and EtCO2 changes precede the development of AMS and result in brain dysfunction and compensatory mechanisms which can be measured by EEG and TCD, respectively. Contrary to our hypothesis, we found that subjects who later developed symptoms of AMS between 3,440 m and 5,050 m altitude exhibited an increase of slow cerebral activity in the right temporal region already at 3,440 m. Cerebral blood flow increased in these mountaineers in the right middle cerebral artery at 5,050 m. These findings indicate that regional brain dysfunction, which can be documented by EEG, heralds the appearance of clinical symptoms of AMS.