Ventilation varies as a function of state, being higher during wakefulness (as indicated by alpha electroencephalogram activity) than during sleep (theta activity). A recent experiment observed a progressive increase in the magnitude of these state-related fluctuations in ventilation over the sleep-onset period (28). The aim of the present experiment was to test the hypothesis that this effect resulted from chemical (feedback-related) amplification of state effects on ventilation. A hyperoxic condition was used to eliminate peripheral chemoreceptor activity. It was hypothesized that hyperoxia would reduce the amplification of changes in ventilation associated with electroencephalogram state transitions. Ventilation was measured over the sleep-onset period under both hyperoxic and normoxic conditions in 10 young healthy male subjects. Sleep onsets were divided into three phases. Phase 1 corresponded to presleep wakefulness; and phases 2 and 3 corresponded to early and late sleep onset, respectively. The magnitudes of state-related changes in ventilation during phases 2 and 3, and under hyperoxic and normoxic conditions were compared using a phase by condition analysis of variance. Results revealed a significant phase by condition interaction, confirming that hyperoxia reduced the amplification of state-related changes in ventilation by selectively decreasing the magnitude of phase 3 state changes in ventilation. However, some degree of amplification was evident during hyperoxia, thus the results demonstrated that peripheral chemoreceptor activity contributed to the amplification of state-related changes in ventilation but that additional factors may also be involved.