The role of GABAergic mechanism in the convulsant effect of mefloquine was investigated in mice. Mefloquine dose dependently induced tonic seizures in mice. Aminooxyacetic acid, diaminobutyric acid and muscimol significantly protected mice against mefloquine-induced seizures by significantly delaying the onset and decreasing the incidence of the seizures. Bicuculline and picrotoxin significantly enhanced the seizure producing effect of mefloquine and also significantly antagonised the protective effect of muscimol against the seizures. Phenobarbitone and diazepam effectively protected mice against mefloquine-induced seizures. Phenytoin did not alter mefloquine-induced seizures. These data indicate that GABA mechanisms might be involved in seizures produced by mefloquine in mice.