Early postnatal freeze lesions in rat neocortex produce anatomic abnormalities resembling those observed in human patients with seizure disorders. Although in vitro brain slices containing the lesion are hyperexcitable, the mechanisms of this alteration have yet to be elucidated. To test the hypothesis that changes in postsynaptic inhibitory receptors may underlie this hyperexcitability, we examined properties of γ-aminobutyric acid type A receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents (mIPSCs). Recordings were obtained in layer II/III pyramidal cells located 1-2 mm lateral to the lesion, mIPSC peak amplitude and rate of rise were increased relative to nonlesioned animals, whereas decay time constant and interevent interval were unaltered. Bath application of zolpidem at a concentration (20 nM) specific for activation of the type 1 benzodiazepine receptor had no significant effect on decay time constant in six of nine cells. Exposure to higher concentrations (100 nM) enhanced the decay time constant of all cells tested (n = 7). Because mIPSCs from unlesioned animals were sensitive to both concentrations of zolpidem, these results suggest that freeze lesions may decrease the affinity of pyramidal cell GABA(A)Rs for zolpidem. This could be mediated via a change in α-subunit composition of the GABA(A)R, which eliminates the type 1 benzodiazepine receptor.