Abstract: This study was undertaken to evaluate the anticonvulsant and analgesic effects of Harpephyllum caffrum stem-bark aqueous extract (HCE) in mice. The anticonvulsant effect of the plant’s stem-bark extract (HCE, 50-800 mg kg-1 intraperitoneally) was examined against pentylenetetrazole (PTZ)- and picrotoxin (PCT)- induced seizures, while the analgesic effect of the extract (HCE, 50-800 mg kg-1 I. p.) was evaluated by hot-plate and acetic acid analgesic test methods. H. caffrum stem-bark extract (HCE, 100-800 mg kg-1 I. p.) dose-dependently and significantly delayed (p<0.05-0.001) the onset of the seizures and profoundly antagonized, PTZ- and PCT-induced seizures. Moreover, HCE (50-800 mg kg-1 I. p.) produced dose-dependent, significant analgesic effects (p<0.05-0.001) against thermally and chemically-induced nociceptive pain in mice. The findings of the present study appear to suggest that H. caffrum stem-bark aqueous extract produces its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain. The results also seem to suggest that H. caffrum stem-bark extract possesses centrally- and peripherally-mediated analgesic properties. Although the precise mechanisms of the anticonvulsant and analgesic actions of HCE could not be established, the findings of this laboratory animal study indicate that H. caffrum stem-bark aqueous extract possesses anticonvulsant and analgesic properties. These findings lend pharmacological credence to the suggested folkloric, ethnomedical uses of the plant as a natural supplementary remedy in the management or control of childhood convulsions and epilepsy, as well as in the treatment or management of painful conditions in some rural communities of South Africa.