Arsenic, a naturally occurring element, is present in food, soil, air and water. All human populations are exposed to arsenic and its compounds through occupational or environmental processes. Since arsenic compounds have been shown to exert their toxicity chiefly by generating reactive oxygen species, we have evaluated the effect of ascorbic acid and a-tocopherol on oxidative damage, antioxidant status and on xenobiotic metabolizing systems in arsenic-exposed rat liver and kidney microsomes. Arsenic exposure increases oxidative damage to lipids and proteins and decreases the levels of antioxidants and the activities of xenobiotic metabolizing enzymes. Coadministration of ascorbic acid and a-tocopherol to arsenic-exposed rats resulted in a reduction in the levels of lipid peroxidation, protein carbonyls and hydrogen peroxide and an elevation in the levels of reduced glutathione, ascorbic acid and a-tocopherol. Ascorbic acid and a-tocopherol treatment decreases the activity of haem oxygenase, whereas it increases the levels/ activity of cytochrome P450, cytochrome b₅ and NADPH-cytochrome P450 reductase in arsenic-intoxicated rats. The results of this study provide evidence that ascorbic acid and a-tocopherol supplementation can improve the arsenic-induced altered microsomal functions in liver and kidney.