The effects of two protein synthesis inhibitors, cycloheximide and anisomycin, were tested on seizures induced by coadministration of lithium and pilocarpine to rats. Systemic cycloheximide (2 mg/kg, sc) and centrally administered anisomycin (300 mu g/10 mu l, icv) doubled the latency to initiation of seizures and to status epilepticus, while peripherally administered anisomycin (50 mg/kg, sc) completely blocked lithium-pilocarpine seizures. These results indicate that protein synthesis is required for initiation of seizures. (C) 1994 Academic Press, Inc.