The distribution of the mRNAs encoding the gamma 2S and gamma 2L subunits of the GABAA receptor in the rat brain has been revealed by in situ hybridization, northern blot and dot blot analysis using specific antisense oligonucleotides. In addition, the quantitative distribution of the gamma 2S and gamma 2L subunit peptides participating in the fully assembled GABAA receptors/benzodiazepine receptors has been mapped by immunoprecipitation with specific anti-gamma 2S and anti-gamma 2L antibodies. Several neuronal types and brain regions are enriched in gamma 2L such as neurons of the layer II of striate cortex and cerebellar Purkinje cells as well as the inferior colliculus, superior colliculus, deep cerebellar nuclei, medulla and pons. Other neuronal types and regions are enriched in gamma 2S such as the mitral cells of the olfactory bulb, pyramidal neurons of the pyriform cortex, layer VI of the neocortex, granule cells of the dentate gyrus and pyramidal cells of the hippocampus. Other cortical areas and cerebellar granule cells express both gamma 2S and gamma 2L in comparable amounts. There is a good correlation between the relative expression of gamma 2S and gamma 2L mRNAs and the relative presence of these protein subunits in fully assembled and mature receptors in the studied brain regions. The differential distribution of gamma 2S and gamma 2L might result in differential ethanol sensitivity of the neurons expressing these GABAA receptor subunits.