The majority of hippocampal interneurons strongly express GABAA receptors containing the α1 subunit, suggesting that inhibitory control of interneurons is important for proper function of hippocampal circuits. Here, we investigated with immunohistochemical and electrophysiological techniques how these GABAA receptors are replaced in mice carrying a targeted deletion of the α1-subunit gene (α10/0 mice). Using markers of five major populations of CA1 interneurons (parvalbumin, calretinin, calbindin, neuropeptide Y and somatostatin), we show that these interneurons remain unaffected in α10/0 mice. In triple immunofluorescence staining experiments combining these markers with the GABAA receptor α1, α2 or α3 subunit and gephyrin, we demonstrate a strong increase in α3- and α2-GABAA receptors clustered at postsynaptic sites along with gephyrin in most CA1 interneurons in α10/0 mice. The changes were cell type-specific and resulted in an increased number of GABAergic synapses on interneurons. These adjustments were mirrored functionally by retention of spontaneous IPSCs with prolonged decay kinetics, as shown by whole-cell patch-clamp recordings of CA1 interneurons. However, a significant decrease in frequency and amplitude of miniature IPSCs was evident, suggesting reduced affinity of postsynaptic receptors and/or impaired vesicular GABA release. Finally, to assess whether these compensatory changes are sufficient to protect against a pathological challenge, we tested the susceptibility of α10/0 mice against kainic acid-induced excitotoxicity. No genotype difference was observed in the effects of kainic acid, indicating that the absence of a major GABAA receptor subtype is functionally compensated for in hippocampal interneurons by a reorganization of inhibitory circuits.