Striatal function in partial seizure development induced by low frequency cortical stimulation of the ipsilateral premotor cortex was investigated by either electrolytic lesion placement or microinjection of putative neurotransmitter-related drugs into the ipsilateral striatum. Unilateral striatal lesioning and intrastriatal injection of muscimol, a GABA-agonist, and glutamic acid diethylester, a presumed antagonist for glutamatergic neurotransmission, were effective in suppressing seizure development, whereas intrastriatal injection of a subconvulsive dose of carbamylcholine chloride (carbachol), a cholinergic agonist, decreased the seizure threshold. In contrast to the ipsilaterally dominant metabolic activation in the intact animal, an inverse asymmetry due to a considerable reduction of deoxyglucose uptake in the ipsilateral thalamus, entopeduncular nucleus, substantia nigra, striatum and surrounding cortex of the focus was found in those brains with striatal lesion. Altogether, the findings suggest that experimental reduction of the inhibitory striatal outputs to both the entopeduncular nucleus and the substantia nigra enhances tonic activities of the projection GABAergic neurons in those nuclei, thereby inhibiting seizure development.