Involvement of the GABAergic nigro-collicular pathway in the control of audiogenic seizures was examined in genetically sensitive rats by studying the effects of bilateral injections into the substantia nigra of muscimol, a γ-Aminobutyric acid (GABA) agonist, and those of bilateral injections into the superior colliculus of picrotoxin, a GABA antagonist, and of muscimol. Microinjections of muscimol (20-80 ng/side) into the substantia nigra and microinjections into the superior colliculus of picrotoxin (20 and 40 ng/side) both failed to suppress audiogenic seizures. Following injections into the superior colliculus, audiogenic seizures were in fact facilitated by picrotoxin and suppressed by muscimol. These results suggest that the nigro-collicular GABAergic pathway is not involved in the inhibitory control over audiogenic seizures. Conversely, a different GABAergic mechanisms may be involved in the superior colliculus in the control of this form of epilepsy. © 1990.