A number of herbal compounds with direct antioxidant activity slow the onset, or completely block, the occurrence of seizures. This increase in latency has been proposed to be due to the antioxidant activity. This hypothesis was directly tested by determining the effects of Trolox, a vitamin E analog, vitamin C, melatonin, and alpha-lipoic acid on the latency to acute seizures induced with pilocarpine, kainic acid, or subcutaneous pentylenetetrazol (PTZ) in adult rats. Trolox, vitamin C, and alpha-lipoic acid had significant anticonvulsant activity against pilocarpine, but there were no acute changes in reduced glutathione levels at 15 or 120 minutes. Other than reduced mortality with vitamin C in the PTZ model, none of the antioxidants had a significant effect against PTZ- or kainic acid-induced seizures. The lack of consistent anticonvulsant effect suggests that the antioxidant activity of the herbal preparations cannot account for the delay in seizure onset.