The naturally occurring progesterone metabolites 5β-pregnan-3α-ol-20- one and 5β-pregnane-3, 20-dione reversibly enhance membrane currents elicited by locally applied GABA in bovine adrenomedullary chromaffin cells. Such potentiation was not influenced by the benzodiazepine antagonist Ro 15-1788. At concentrations in excess of those necessary to evoke potentiation of GABA currents, 5β-pregnan-3α-ol-20-one and 5β-pregane-3, 20-dione directly activated a membrane conductance. The resulting currents were potentiated by phenobarbitone and diazepam, and abolished by the GABA A -receptor antagonist, bicuculline. On out­side-out membrane patches, 5β-pregnan-3a-ol-20-one and 5β-pregnane-3, 20-dione activated single channel currents of similar amplitude to those evoked by GABA. The results suggest that certain naturally occurring steroids potentiate the actions of GABA and, additionally, directly activate the GABA A receptor.