The effects of microinjection of various neuroactive compounds into the anterior thalamic nucleus (AN) and other selected subcortical regions of guinea pig brain on the expression of pentylenetetrazol (PTZ)-induced behavioral and electrical seizure activity were examined. Excitatory agents, kainic acid (KA), bicuculline (BIC) or PTZ, injected into the AN or other thalamic nuclei, striatum, but not the mammillary bodies (MB), facilitated the EEG convulsant action of systemically administered PTZ. Injection of muscimol into the AN protected against the expression of PTZ-induced repetitive high-voltage EEG seizure discharges and inhibited the facilitatory effects of subcortically applied KA or BIC. Injection of muscimol into the AN was also able to terminate established ongoing seizure discharges. Unilateral application of muscimol to the AN did not prevent the repetitive hypersynchronous EEG discharges following systemic PTZ but did result in the delay in the onset of cortical hypersynchrony in the ipsilateral hemisphere. Muscimol injections into other thalamic nuclei, MB, cortex, striatum or directly into the CSF space had no anticonvulsant effect, however. Microinjection of gamma-vinyl-gamma-aminobutyric acid, a selective GABA transaminase inhibitor, resulted in protection from the behavioral convulsant action and lethal effects of PTZ when administered into the thalamus, especially the AN, but not when injected into the striatum or CSF. These data demonstrate that the AN is an important subcortical nucleus for the mediation of both cortical EEG synchrony and behavioral seizure expression induced by PTZ. In light of previous results establishing a role for the brainstem and diencephalon in PTZ seizure expression, the AN may serve, in part, as a gating mechanism for the propagation of paroxysmal activity between subcortical areas and the cerebral cortex.