Involvement of gamma-aminobutyric acid (GABA)-mediated function in epileptogenesis was studied in rat hippocampal slices, in which repetition of high-frequency electrical stimulation induced afterdischarges (ADs) to create an in vitro model for ictal activity. A GABAA receptor antagonist, bicuculline, fully blocked the ADs. On the other hand, the presence of bicuculline caused single stimuli to evoke short-duration epileptiform bursts, a well-known model for interictal activity. Therefore, we conclude that activation of GABAergic function appears to be necessary for ictal activity, while its dysfunction induces interictal activity, and propose a modification to the simple disinhibition hypothesis for epileptogenesis.