In a particular brain region specific changes in inhibition or excitation may be the basis of seizure initiation. Alternatively, changes in the balance of excitation and inhibition in the circuit, which may be detectable as polysynaptic responses may be more important indicators of epileptogenesis. That the appearance of polysynaptic responses precedes the initiation and, therefore, may be necessary for the onset of epileptiform activity in the hippocampal-parahippocampal circuit was tested using the chemical convulsant pentylenetetrazol. Excitation and paired-pulse inhibition were measured in CA1 and the dentate gyrus of the urethane-anaesthetized rat before and after administration of pentylenetetrazol. In addition, three polysynaptic responses were monitored. In both CA1 and the dentate gyrus, pentylenetetrazol, 100 mg/kg, caused a trend towards increased excitability and caused a relatively mild loss of inhibition. Two polysynaptic responses appeared in the dentate gyrus after the administration of pentylenetratrazol, both apparently mediated through the entorhinal cortex. A polysynaptic response of the CA1 pyramidal neurons to contralateral angular bundle stimulation was not observed. These experiments demonstrate that pentylenetetrazol will facilitate only the appearance of polysynaptic responses mediated through the entorhinal cortex. These results support the hypothesis that pentylenetetrazol has a specific action within the entorhinal cortex that may facilitate the synchronization and spread of epileptiform activity. These results are also consistent with the hypothesis that the appearance of polysynaptic responses may be necessary for the onset of epileptogenesis in the hippocampal-parahippocampal circuit.