We studied the effects of combined exposure to arsenic and fluoride on (i) brain biogenic amines, oxidative stress and its correlation with glutathione and linked enzymes; (ii) alterations in the structural integrity of DNA; and (iii) brain and blood arsenic and fluoride levels. Efficacy of alpha-tocopherol in reducing these changes was also determined. Male mice were exposed to sodium meta arsenite (50 ppm) and sodium fluoride (50 ppm) individually and in combination for ten weeks. Animals were given vitamin E supplementation (5 mg/kg, i.m., alternate days) throughout the experiment. Exposure to arsenic and fluoride significantly decreased the levels of brain biogenic amines. However; acetyl cholinesterase (AChE) and monoamine oxidase (MAO) activities showed an increase on fluoride exposure. There was also an increase in reactive oxygen species, thiobarbituric acid reactive species level, glutathione S-transferase and glutathione peroxidase activities and decreased superoxide dismutase activity, GSH:GSSG ratio, glucose 6-phosphate dehydrogenase activity. Combined exposure to these toxicants produced more pronounced effects on AChE, MAO, SOD and catalase activities. Infrared spectra showed less toxicity during combined exposure as the characteristic peaks of cytosine and alpha-helical structure of DNA were observed in normal and arsenic plus fluoride-exposed animals. Vitamin E reduced brain fluoride level and tissue oxidative stress but had no effect on arsenic. Combined exposure to arsenic and fluoride does not necessarily lead to more pronounced toxicity and interestingly exhibit some antagonistic effects. Vitamin E supplementation may be of added value in reverting some of the toxic effects.