STUDY OBJECTIVES: Gamma-hydroxybutyrate (GHB) is an endogenous neuromodulator that appears to have wide-ranging effects on vigilance and behavior. In the present study, we examined the effects of GHB on sleep-wake behavior and EEG in mice. In addition, we measured effects of GHB on body temperature and arousal or stress hormones. DESIGN: Adult male BALB/c mice were implanted with electroencephalographic and electromyographic electrodes to record vigilance states and an intraperitoneal transmitter to record body temperature. After recovery from surgery and habituation to the recording procedure, the mice were intraperitoneally injected with saline or GHB (50, 150 or 250 mg/kg) half an hour after light onset. Blood samples to measure effects of GHB on corticosterone and prolactin levels were collected in a separate group of mice. SETTING: N/A PATIENTS: N/A INTERVENTIONS: N/A RESULTS: At the lowest dose, GHB had no conspicuous effects on behavioral vigilance and electroencephalogram, nor on body temperature and endocrine measures. At the 2 higher doses, GHB induced a short period of electroencephalographic hypersynchrony in parallel to complete behavioral inactivity, an unnatural flat body posture, and nonresponsiveness to stimulation. After the highest dose of GHB, this state of reduced vigilance was associated with a decrease in body temperature, while prolactin and corticosterone levels were strongly increased. CONCLUSIONS: The results do not indicate a clear sleep-promoting effect of GHB in mice, but, at higher doses, it caused electroencephalographic hypersynchronization together with a coma-like state.