Previous study revealed that bursting activity generated by a variety of means in slices of piriform cortex induces persistent epileptiform EPSPs in superficial pyramidal cells by an NMDA-dependent process. The present study was undertaken to test the hypothesis that the observed epileptiform EPSPs in superficial pyramidal cells are driven by deep cells. This hypothesis was suggested by recent findings from in vitro studies of the properties of deep cells and in vivo studies indicating that the deep part of the piriform cortex or neighboring deep structures are involved in the generation of seizure activity in animal models of epilepsy. Results from simultaneous cell-pair recordings, examination of subdivided slices, and local application of excitatory and inhibitory agents provided strong evidence in support of this hypothesis. It was concluded that the endopiriform nucleus, a collection of cells immediately deep to the piriform cortex, plays a central role in generation, but that cells in the deep part of layer III and the claustrum may also contribute. Furthermore, it was found that generation of prolonged ictal-like activity only occurs in slices of piriform cortex in which the endopiriform nucleus is present. Implications of these findings for epileptogenesis are discussed.