gamma-Hydroxybutyrate, a naturally occurring substance present in the mammalian central nervous system caused a dose-dependent (0.25-10 mM) hyperpolarization and small membrane conductance increase when applied to hippocampal CA1 pyramidal neurones in vitro. This action was reversibly inhibited by the GABAB antagonist, CGP 35348 (20-100 microM) and divalent cations, Zn2+ and Ba2+, but not by the GABAA antagonist bicuculline (50 microM). These results suggest that GABAB receptors may mediate the actions of gamma-hydroxybutyrate.