Taurine, an inhibitory amino acid, potently acts on a subclass of gamma-aminobutyric acid type A (GABAA) receptors. Taurine competitively inhibits [3H]muscimol binding to purified GABAA receptors with an average IC50 value of 50 microM, and enhances [3H]flunitrazepam binding to GABAA-linked benzodiazepine receptors with an EC50 of about 10 microM and with maximal extent lower than that for GABA. Taurine shows variable affinities (low micromolar to near millimolar) for muscimol binding sites in different brain regions as measured by autoradiography. The taurine-sensitive GABA sites are enriched in dentate gyrus, substantia nigra, cerebellum molecular layer, median thalamic nuclei, and hippocampal field CA3; these areas are also enriched in mRNA for the GABA-binding beta 2 subunit subtype. Taurine shows differential affinities for the multiple muscimol-GABA binding polypeptides present in purified GABAA receptors, notably a higher affinity for a beta 55 than a beta 58 polypeptide; these probably represent beta 2 and beta 3 clones, respectively. This work defines a significant target of taurine's inhibitory activity as some GABAA receptor GABA sites, lending support to the hypothesis that this endogenous substance may have a physiological action.