In the lithium-pilocarpine model (li-pilocarpine) of temporal lobe epilepsy, GABAA receptor-mediated inhibitory postsynaptic currents (GABAA IPSCs) were recorded in dentate gyrus granule cells (GCs) from adult rat hippocampal slices. The properties of GABAA IPSCs were compared before and after superfusion of modulators in control conditions (li-saline rats) and in li-pilocarpine rats 24-48 h and 3-5 months (epileptic rats) after status epilepticus (SE). The mean peak amplitude of GABAA IPSCs increased by about 40% over li-saline values in GCs 24 to 48 h after SE and remained higher in epileptic rats. In li-pilocarpine rats, studied at 24-48 h after SE, diazepam (1µM) lost 65% of its effectiveness at increasing the half-decay time (T50%) of GABAA miniature IPSCs (mIPSCs). Diazepam had no effects on mIPSC T50% in epileptic rats. The benzodiazepine ligand, flumazenil (1µM), acting as an antagonist in li-saline rats, exhibited a potent inverse agonistic effect on GABAA mIPSCs of GCs from li-pilocarpine rats 24-48 h and 3-5 months after SE. The neurosteroid, allopregnanolone (100 nM), which considerably prolonged GABAA mIPSCs in li-saline rats, totally lost its effect in rats studied 24-48 h after SE. However, this decrease in effectiveness was transient and totally restored in epileptic rats. In addition to the up-regulation in the number of receptors at individual GC synapses, we propose that these "epileptic" GABAA receptors possess benzodiazepine binding sites with altered allosteric properties. The failure of benzodiazepine and neurosteroid to potentiate inhibition early after SE may be a critical factor in the development of epileptogenesis and occurrence of seizures.