The study of neuronal network synchronization in epileptic animals is rather difficult when using in vitro brain slices and it is generally made possible by the use of convulsive agents or buffers. In this study we report that epileptiform discharges occur spontaneously (duration= 2.60±0.49 s) or can be induced by electrical stimuli (duration= 2.50±0.62 s) in the entorhinal cortex (EC) of brain slices obtained from pilocarpine-treated rats but not in those from age-matched, non-epileptic control (NEC) animals. These network-driven epileptiform events consist of field oscillatory sequences at frequencies greater than 200 Hz that most often initiate in the lateral EC and propagate to the medial EC with 4-63 ms delays. The NMDA receptor antago¬nist CPP depresses the rate of occurrence (p<0.01) of these spontaneous epileptiform discharges but fails in blocking them. Paradoxically, stimulus-induced epileptiform responses are enhanced in duration during CPP application. However, concomitant application of NMDA and non-NMDA glutamatergic antagonists abolishes spontaneous and stimulus-induced epileptiform events. Intracellular recordings from lateral EC layer V cells indicate a lower frequency of spontaneous hyperpolarizing post-synaptic potentials in pilocarpine-treated tissue than in NEC (p<0.002) both under control conditions and with glutamatergic receptor blockade; the reversal potential of pharmacologically isolated GABAA receptor-mediated inhibitory post-synaptic potentials has similar values in the two types of tissue. Finally, immunohistochemical analysis shows that parvalbumin positive interneurons are selectively reduced in number in EC deep layers. Collectively, these results indicate that reduced inhibition within the pilocarpine-treated EC layer V may promote network epileptic hyperexcitability.