Labeling of the two more important gamma-aminobutyric acidA (GABA(A)) supramolecular sites with [3H] muscimol (GABA(A)) and [3H] flunitrazepam (benzodiazepine) provided saturable, stable, and dimorphic binding activities in cortical and limbic regions of the wood mouse Apodemus sylvaticus. Of the cortical layers, which contained the highest [3H] muscimol binding levels, only the female lamina V supplied a greater (51%; P <0.01) receptor density than in the male. Areas of the limbic system instead proved to be the more favorable targets for differential GABA(A) binding levels. The highest (P <0.001) and higher levels were found in the oriens-pyramidalis CA1 layer of the hippocampus (65%) and in the vertical limb diagonal band-medial septal nucleus (48%), basolateral amygdala nucleus (45%), and ventromedial hypothalamic nucleus (43%), respectively, of the female. A similar pattern was obtained for [3H]flunitrazepam binding activity, especially in the presence of GABA. The highest and higher binding activities were obtained in the female central amygdala nucleus (78%) and in the ventromedial hypothalamic nucleus (52%), basolateral amygdala nucleus (48%), and oriens-pyramidalis CA1 layer of the hippocampus (47%), respectively, whereas higher levels were observed only in the male vertical limb diagonal band-medial septal nucleus (56%). Even in the cortical regions, the female exhibited higher (42%; cortex lamina V) and moderately higher (38%; cortex lamina VI) levels, with binding differences in the latter site plus in the basolateral amygdala nucleus occurring in a GABA-nondependent manner. From the saturation binding analyses it was possible to reveal that both maximal number of binding sites (Bmax) and mean dissociation constant (K(D)) modifications were responsible for receptor differences of the two GABAergic sites. These findings tend to suggest that dimorphic variations of the GABA(A) supramolecular sites, in some cortical and limbic regions, are strongly involved in sex-specific aggressive and reproductive activities of rodents living in their natural habitats.