Abstract: The anticonvulsant activity of Zanthoxylum capense (Thunb.) Harv. (Rutaceae) was investigated by studying the effects of the leaf methanol and aqueous extracts on seizures induced by pentylenetetrazole, bicuculline, picrotoxin, N-methyl-DL-aspartic acid and strychnine in mice. Both methanol and aqueous extracts of Z. capense significantly antagonized (p<0.05-0.005) seizures induced by pentylenetrazole (PTZ), picrotoxin and strychnine. Methanol extract of Z. capense significantly antagonized (p<0.05) bicuculline-induced seizures while the aqueous extract significantly delayed (p<0.001) the onset of the seizures. Both methanol and aqueous extracts of the plant species significantly delayed (p<0.05-0.005) the onset of N-methyl-DL-aspartic acid (NMDLA)-induced seizures. Phenobarbitone and diazepam significantly antagonized (p<0.001) seizures induced by PTZ, bicuculline and picrotoxin but did not alter NMDLA-induced seizures. Phenobarbitone significantly attenuated (p<0.01) strychnine-induced seizures. Phenytoin or dimethylsulfoxide did not alter the seizures induced either by PTZ, bicuculline, picrotoxin, NMDLA or strychnine to any extent. The LD50 value obtained following oral administration of both the leaf aqueous and methanol extracts of Z. capense was above 3200 mg kg-1 and that obtained after intraperitoneal administration was 283.6 mg kg-1. The phytochemical analysis of the plant species revealed the presence of alkaloids, triterpene steroids, reducing sugars, saponins, tannins and quinones. The data obtained indicate that the leaf methanol and aqueous extracts of Z. capense have anticonvulsant activity which may probably involve both GABAergic, glutaminergic and glycinergic mechanisms. The relatively high LD50 value obtained following oral administration of the plant extract shows that it is non-toxic and /or safe in mice.