Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5H-imidazo-2,1-a-isoindole) although not chemically related to the phenylethylamine group, shows a pharmacological profile similar to that of amphetamines. In rats these anorectic drugs enhance dopamine (DA) turnover, which is the mechanism that causes anorexia. It has been hypothesized that amphetamine causes a long-lasting depletion of DA, a decrease of dopaminergic transport pumps and nerve terminal degeneration increasing. These actions provide a cellular environment encouraging the autoxidation of DA that may lead to lipid peroxidation and neuronal damage. Considering that both drugs may cause neuronal damage by oxidative mechanisms, this study was conducted to investigate the action of mazindol and methamphetamine on brain cell antioxidant defense system and to investigate whether animal age is important in the antioxidant response to chronic anorectic administration. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the total glutathione (GSH) content in brains of rats, were measured. The animals (2 groups with 5 and 18 months old) were treated for 5 months (i.p.) with mazindol (10 mg/kg body weight/day), methamphetamine (2.5 mg/kg body weight/day) or saline. The results obtained showed no differences between SOD, CAT, GPx activities and GSH content in the brain of animals treated with saline compared with both drugs, either in 10-month or 23-month groups. On the other hand, brain total GSH content of old animals was found to be lower than that from young ones, independent of the treatment. SOD activity was found to be increased, CAT unchanged and GPx decreased, in the brain of old animals, treated with both drugs or saline. These findings led us to conclude that the chronic administration of mazindol and methamphetamine have no effects on the antioxidant systems studied either in young (10 months) or in old (23 months) rats.