The functional relationship between the substantia nigra (SN) and the area tempestas (AT), an epileptogenic site in the deep prepiriform cortex, was investigated. Stimulation of GABA receptors in SN with muscimol, or blockade of nigral excitatory amino acid receptors with 2-aminophosphonoheptanoic acid (AP7), protected against convulsions evoked by the unilateral focal injection of bicuculline in the AT. The protective effects were obtained only with bilateral nigral injections; unilateral manipulations were without anticonvulsant effect. Bilateral intranigral morphine did not exert an anticonvulsant effect against convulsions evoked from the AT, although this treatment induced stereotyped sniffing and gnawing behavior similar to that evoked by intranigral muscimol and AP7. The data indicate that seizures evoked from the AT of one hemisphere are susceptible to suppression by inhibition in the SN, but only when the inhibition occurs in the SN of both hemispheres. This suggests that the seizure suppressant action evoked from the SN is exerted during the course of the propagation of the seizure, once it has spread bilaterally.