The effects of intraperitoneal administration of the anticonvulsants phenytoin and sodium valproate were compared with ethosuximide on maximal electroshock seizure-related changes in rat hippocampal gamma-aminobutyric acid (GABA) and glutamate release in vivo as measured by microdialysis. There were immediate increases in GABA and glutamate in the 5 min post-ictal period, followed by a sustained reduction in GABA levels. Glutamate levels, however, were subsequently reduced until 20 min post-ictal before gradually increasing above basal. All animals displayed tonic hind-limb extension that was blocked by phenytoin (20 mg/kg) and sodium valproate (400 mg/kg) but not ethosuximide (150 mg/kg). Phenytoin attenuated the immediate post-ictal increase observed in glutamate whilst sodium valproate enhanced GABA release and prevented its secondary post-ictal inhibition. Ethosuximide was without effect on the post-ictal changes. These are the first data to show detailed seizure-induced amino acid changes and the in vivo effects of anticonvulsants on them in the seizure model.