Cell membranes isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE) are injected into frog oocytes. Within few hours the oocytes acquire functional g-aminobutyric acid type A receptors (GABAAR) and the GABA evoked currents display marked run-down during repetitive applications of the neurotransmitter. In contrast, GABAAR function is stable upon repetitive applications of GABA in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic or ischemic temporal lesions (lesional TLE, LTLE). It was found that this use-dependent GABAAR run-down develops also in pyramidal neurons of TL neocortical slices, while TL pyramidal neurons from neocortical slices of a traumatic LTLE patient do not show GABAAR run-down. Preliminary results in oocytes expressing "epileptic" GABAA receptors show that the run-down could be reduced by endocytosis inhibitors, concanavalin-A and primaquine. We speculate that the use-dependent functional instability of neocortical GABAAR represents a TLE-specific dysfunction and is due to an increase of receptor endocytosis.