The effects of chronic administration of alpha-tocopherol or melatonin, or acute ascorbic acid administration on the convulsant action of methylmalonic acid (MMA) were investigated in adult male rats. Animals were chronically injected with alpha-tocopherol (40 mg kg(-1), i.p.), melatonin (5 mg kg(-1), i.p.) or vehicle for 7 days. Buffered MMA (6 micromol/2 microl) or NaCl (9 micromol/2 microl) was injected intrastriatally and the animals were observed for the appearance of clonic or tonic-clonic convulsions and rotational behavior. Ascorbic acid (100 mg kg(-1), s.c.) was administered 30 min before MMA injection. Alpha-tocopherol and ascorbic acid pretreatment decreased the duration of the convulsive episodes and the rotational behavior elicited by MMA. This study provides evidence that free radical generation may participate in the convulsant effects of methylmalonic acid.