The effects of gamma-hydroxybutyrate have been studied on the membrane properties of pars compacta neurons within the guinea-pig substantia nigra maintained in vitro. The effects of gamma-hydroxybutyrate are to (i) lower input resistance, (ii) hyperpolarize the cell membrane in a dose-dependent manner and (iii) facilitate calcium conductances. These effects are resistant to the blockade of sodium channels with tetrodotoxin and blockade of potassium channels with tetraethylammonium or 4-aminopyridine. Furthermore, these effects are only partially blocked by high doses of the GABA receptor antagonist bicuculline: indeed the effects of the GABA receptor agonist muscimol can be differentiated from those of gamma-hydroxybutyrate in that the latter is sensitive to application of barium ions. The results suggest that gamma-hydroxybutyrate acts to increase utilization of calcium, which in turn leads to an initiation of calcium-dependent events. The functional consequences of these effects of gamma-hydroxybutyrate are discussed with regard to its possible endogenous modulatory actions.