In the presence of either hypocapnia or sleep, hypoxia has been shown to induce periodic breathing and increase the total variational activity of breath components. It is not known whether hypoxia induces alterations in breathing variability during wakefulness and in the absence of hypocapnia. To address this issue, we studied nonobtrusively 14 healthy awake subjects before and during the delivery of a hypoxic gas mixture via a plastic hood; the subjects' oxygen saturation decreased from 98 to 79% and end-tidal carbon dioxide tension was kept constant. Compared with air, isocapnic hypoxia increased the gross variability of minute ventilation (V I), tidal volume (VT), inspiratory time (TI), and expiratory time (TE) (all p < 0.004). Isocapnic hypoxia decreased the autocorrelation coefficient at a lag of one breath for TE (p < 0. 008) and V I (p = 0.07), the number of consecutive breath lags having significant autocorrelation coefficients for TE (p = 0.03), and the cycle time of oscillations in V I (p = 0.03). When partitioned, the increase in total variational activity during isocapnic hypoxia was found to result from increases in the random fractions of V I, VT, TI, and TE (all p < 0.05), and the oscillatory fractions of V I, VT, and TE (all p < 0.03). In conclusion, hypoxia induced hidden oscillations in V I, VT, and TE despite wakefulness and an isocapnic state, suggesting that neural responses may have a more important role in the genesis of hypoxia-induced oscillations than previously reported.