Muscimol is a potent agonist at GABA-inhibitory synapses in mammalian brain. Given systemically at 7 mumol per kilogram, it blocks topical penicillin seizures and delays the onset of generalized metrazol convulsions in rats. It has no effect against generalized seizures caused by picrotoxin or strychnine. Higher doses of muscimol cause bradykinesia, ataxia, catatonic posturing, and slowing of the electroencephalogram. When applied topically to cortex, muscimol blocks focal penicillin, bicuculline, and picrotoxin discharges in a dose-response relationship. It has no effect against topical strychnine. Muscimol offers a potential new approach to the treatment of epilepsy.