The effect of intravenous administration of gamma-hydroxybutyric acid (GHB) (50-400 mg/kg) on the firing rate of substantia nigra pars reticulata (SN-PR) neurons was studied by making single cell extracellular recordings in unanesthetized rats. For comparison, the effect of intravenous muscimol (0.5-2 mg/kg) and ethanol (0.5-2 g/kg) was also studied. GHB produced variable effects: dose-related inhibition in 7 out of 18 (38.8%) neurons and no significant change in 11 out of 18 (61.2%) neurons tested. In contrast, muscimol and ethanol produced a dose-related inhibition of the SN-PR firing rate. The results indicate that GHB, unlike muscimol and ethanol, has no profound effect on the activity of SN-PR neurons, and thus disinhibition of dopaminergic units, through inhibition of SN-PR neurons, is probably not the mechanism by which GHB stimulates the firing rate of dopaminergic neurons.