In this work, the protective effect of Vitamin E plus selenium (Vit E + Se) and melatonin against 7,12-dimethylbenz(a)anthracene (7,12DMBA)-induced changes in superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT) and carbonic anhydrase (CA) activities and malonedialdehyde (MDA) levels of mouse brain were compared. 12-month old mice were divided into four groups each including 10 animals. The first group served as control group. The second group was treated with 7,12-DMBA (20 mg/(kg day)). The third group was treated with 7,12-DMBA and Vitamin E (90 mu g/(individual day)) and selenium (1.8 mu g/(individual day)) simultaneously. The fourth group was treated with 7, 12-DMBA and melatonin (4.2 mg/(kg day)) simultaneously. Treatment continued for 21 days after which the mice were sacrificed and brain homogenates were prepared. 7,12-DMBA treated group exhibited significantly decreased levels of brain SOD, GSHPx, CAT and CA activities and increased MDA levels as compared to control. Vitamin E + Se fully or partially restored enzyme inhibition except for SOD. Lipid peroxidation was also reduced in Vitamin E + Se treated group. Melatonin provided a better protection for SOD, GSHPx and CAT, and a plausible protection for CA activity. Protection against lipid peroxidation measured as MDA in melatonin treated group was appreciable although slightly lesser than the protection provided by Vitamin E + Se. The results imply that Vitamin E + Se and melatonin both provide chemoprevention against 7,12-DMBA-induced oxidative stress in mouse brain. (c) 2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.