The anticonvulsant activity of the selective group II metabotropic glutamate receptor (mGlu) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been evaluated in chemoconvulsant and sound-induced models of epileptic seizures in DBA/2 mice. 2R,4R-APDC (≥10 nmol, intracerebroventricularly (i.c.v.), −15 min) transiently reduced sound-induced seizure activity including clonic seizures to 40% of vehicle at 20 nmol (i.c.v.) and 30% of vehicle at 100 mg/kg (intraperitoneally (i.p.), −15 min). 2R,4R-APDC inhibited clonic seizures induced by the group III mGlu antagonist (R,S)-α-methylserine-O-phosphate (2.5 μmol, i.c.v.) when co-injected at 20–40 nmol and inhibited limbic seizure activity induced by the mGlu 1/5 agonist (R,S)-3,5-dihydroxyphenylglycine (1.5 μmol, i.c.v.) when co-injected at 10–40 nmol. A reversal of the anticonvulsant activity of 2R,4R-APDC was observed at (>20 nmol) in each of the chemoconvulsant and sound-induced models of epileptic seizures. 2R,4R-APDC (0.1–1 μmol, i.c.v.) induced stimulus-independent, rapid and dose-dependent clonic seizures. Selective mGlu 2/3 agonists represent a novel class of potential anti-epileptic drugs, however due to the proconvulsant activity observed here, 2R,4R-APDC is obviously limited in this regard.