The identification of a large variety of GABAA receptor subunits by molecular cloning suggests the existence of multiple receptor subtypes differing in localization and functional properties. In the present study we analysed immunohistochemically the cellular distribution of GABAA receptors containing the alpha 1 subunit in the rat hippocampus with a subunit-specific antiserum. Prominent staining of numerous interneurons was evident in Ammon's horn and the dentate gyrus, which contrasted with moderate and diffuse immunoreactivity in the dendritic layers of pyramidal and granule cells. Double immunofluorescence staining with antibodies to GABA revealed that a subset of GABAergic neurons in the hippocampus were immunoreactive for the alpha 1 subunit. To determine whether these cells represent distinct subpopulations of interneurons, we analysed the co-localization of the GABAA receptor alpha 1 subunit with selective markers of hippocampal interneurons (selected calcium-binding proteins and neuropeptides). In both Ammon's horn and the dentate gyrus, all parvalbumin-positive neurons and 50% of calretinin-positive neurons were double-labelled, whereas interneurons containing calbindin-D28k were devoid of alpha 1 subunit staining. Similarly, most neurons positive for neuropeptide Y and a subset of somatostatin-positive cells were double-labelled, in contrast to cholecystokinin- and vasoactive intestinal peptide-containing cells, which lacked the alpha 1 subunit staining. These results demonstrate cell-specific expression of GABAA receptors containing the alpha 1 subunit among subsets of hippocampal interneurons, pointing to a pronounced functional specialization of these cells. Furthermore, the prominent expression of GABAA receptors by interneurons suggests that disinhibition may be of major functional relevance in regulating the balance between excitation and inhibition in hippocampal circuits.