Hypoxia, a noxious and hyperventilatory stimulus and a modifier of neuronal metabolism, could influence cortical function. In this study we attempted to assess any such influence, its determinants, and particularly the role in it of the accompanying hypoxic emotional distress. We addressed the issue by examining the associations among EEG, ventilation, and anxiety during progressive poikilocapnic hypoxia (end-point SaO(2) approximately 75%) in 12 awake healthy volunteers (mean age 27.5 +/-0.7 yr). All subjects hyperventilated in response to hypoxia and 3 of them had a high level of anticipatory anxiety that forced one person to discontinue the test. We failed to show any major effect of hypoxia on the EEG pattern analyzed by visual inspection or wavelet power spectra. Therefore, no relationship between the ventilatory and cortical activity responses to hypoxia could be established. Cortical activity changes appeared, however, in the subjects who experienced emotional distress during the test. These changes were apparent on an expanded analysis of the EEG signal by the use of the Lempel-Ziv complexity that takes into account the ordering of variations in the signal, rather than only the relative frequency of events analyzed by the Shannon entropy. The Lempel-Ziv complexity offers promise as a novel method for unraveling fine and otherwise unexpressed alterations in cortical bioelectrical activity.