Quantitative autoradiography of rat brain coronal sections show that maximum enhancement (more than 80%) of [3H]flunitrazepam binding by GABA occurs in brain regions particularly rich in type I benzodiazepine receptors (inferior colliculus, medium raphe, central gray and substantia nigra); conversely, brain areas where type II predominates show the lowest enhancement by GABA (about 50%). These results, suggesting that the coupling of GABA receptors with type I sites is more efficient than that with type II sites, are at variance with those reported on GABA-benzodiazepine receptors expressed in transfected cells, where the greater GABA potentiation of benzodiazepine binding is due to a subtype of the type II site containing the alpha 3 subunit of the GABAA receptor. One possible explanation of these discrepancies is that the type II receptors found in type I-enriched tissues (inferior colliculus, median raphe, central gray and substantia nigra) are associated with the alpha 3-subunit, while the type II sites present in limbic and cortical regions represent a subpopulation carrying the alpha 2-subunit of the GABAA receptor, with lower GABA potentiation.