Intrahippocampal injection(ihci) of guanidinosuccinic acid (GSA) to rats, induced typical generarized clonic seizures and epileptiform discharges in electrohippocampogram (EHG) and electrocorticogram (ECoG), degenerative changes of neuronal cells in the injected side hippocampus. The pyramidal cells in CA1 area were found to be more vulnerable to GSA than the granular cells. Phenobarbital and phenytoin are typical antiepiletics, but in no case did they successfully protect against GSA induced convulsions, epileptiform discharges in the EHG and ECoG and neurolysis. Ketamine, a selective noncompetitive NMDA receptor antagonist, was shown to protect against not only seizures, but also neuronal cell damage induced by GSA. All these results indicate that GSA very like the endogenous excitatory amino acid, glutamic acid, it also has such effects mentioned above. Therefore, the NMDA receptor may mediate both effects of GSA.