Previous work has shown that the magnitude of state-related ventilatory fluctuations is amplified over the sleep-onset period and that this amplification is partly due to peripheral chemoreceptor activity, because it is reduced by hyperoxia (J. Dunai, M. Wilkinson, and J. Trinder. J. Appl. Physiol. 81: 2235-2243, 1996). These data also indicated considerable intersubject variability in the magnitude of amplification. A possible source of this variability is individual differences in peripheral chemoreceptor drive (PCD). We tested this hypothesis by measuring state-related ventilatory fluctuations throughout sleep onset under normoxic and hyperoxic conditions in subjects with high and low PCD. Results demonstrated that high-PCD subjects experienced significantly greater amplification of state-related ventilatory fluctuations than did low-PCD subjects. In addition, hyperoxia significantly reduced the amplification effect in high-PCD subjects but had little effect in low-PCD subjects. These results indicate that individuals with high PCD are likely to experience greater sleep-related ventilatory instability and suggest that peripheral chemoreceptor activity can contribute to sleep-disordered breathing.