Extracts of Rhus chirindensis stem-bark are used extensively in South African traditional medicines for the treatment, management and/or control of an array of human ailments, including childhood convulsions and epilepsy. In this study, we investigated the anticonvulsant activity of the plant's stem-bark aqueous extract (RCE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used as reference anticonvulsant drugs for comparison. Single intraperitoneal injections of PTZ (90 mg/kg), PCT(10 mg/kg) or BCL (30 mg/kg) produced tonic-clonic seizures. Like the standard antiseizure drugs used, Rhus chirindensis stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) significantly delayed (p<0.05-0.001) the onset of, and antagonized pentylenetetrazole-induced seizures. The plant's stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) also profoundly antagonized picrotoxin-induced seizures, but only weakly antagonized bicuculline-induced seizures. Although the data obtained in the present study do not provide conclusive evidence, it would appear that RCE produces its antiseizure effect by enhancing GABAergic neurotransmission and/or action in the brain. The results of this laboratory animal study indicate that RCE possesses anticonvulsant activity in the mammalian experimental model used, and thus suggest that the plant may be used as a natural supplementary remedy in the management, control and/or treatment of childhood convulsions and epilepsy. In conclusion, the findings of this study lend pharmacological credence to the suggested folkloric, ethnomedical uses of Rhus chirindensis in the management of childhood convulsions and epilepsy in some rural communities of South Africa.