To study the role of GABA-ergic mechanisms in sleep regulation, the combined action of 40 h sleep deprivation and either 20 mg zolpidem or placebo on the sleep electroencephalogram (EEG) were investigated by quantitative EEG analysis in eight young men who participated in a positron emission tomography study. Compared with baseline, sleep deprivation increased low-frequency (1.25-7.0 Hz) EEG power in non-rapid eye movement (NREM) sleep in the placebo night. After administration of zolpidem, power in the 3.75-10.0 Hz range and 14. 25-16.0 Hz band was reduced. The largest decrease was observed in the theta band. Comparison with placebo revealed that zolpidem attenuated power in the entire 1.75-11.0 Hz range. The plasma concentration of zolpidem at 4.5 h after intake showed a positive correlation with the drug-induced difference in power from placebo in the 14.25-16.0 Hz band. Regional EEG analysis based on bipolar derivations along the antero-posterior axis disclosed, for NREM sleep, a drug-induced posterior shift of power in the frequency range of 7.75-9.75 Hz. Zolpidem did not affect rapid eye movemnt sleep spectra. We conclude that sleep deprivation and agonistic modulation of GABAA receptors have separate and additive effects on power spectra and that their effects are mediated by different neurophysiological mechanisms.