Bilateral focal injections of the serotonin uptake inhibitor, fluoxetine (1.75-7.0 nmol) into substantia nigra (SN) protected against convulsive seizures evoked by the focal injection of bicuculline methiodide into area tempestas, an epileptogenic site within the deep prepiriform cortex. Injection of fluoxetine unilaterally in SN or bilaterally into a site dorsal to SN was not anticonvulsant. Blockade of nigral gamma-aminobutyric acid (GABA) receptors with bicuculline in SN did not reverse the anticonvulsant action of intranigral fluoxetine. These data suggest that serotonergic transmission in SN exerts a seizure suppressing action which is independent of GABA transmission in SN.