In this study, five months old female transgenic (Tg2576) and wild-type mice were exposed for 6 months to aluminum (1mg Al/g diet), melatonin (10mg/kg/day), Al plus melatonin, or vehicle only (control group). General motor activity was evaluated using an open-field, whereas spatial learning and memory were assessed in a water maze. Aluminum levels in hippocampus, cortex and cerebellum were determined. Aluminum-treated Tg2576 mice showed higher Al levels in hippocampus than non-Al treated animals. No Al effects on general motor activity were found, while the open-field test showed an increased number of rearings in Tg2576 mice. A lower habituation pattern was observed in melatonin-treated animals. Differences in learning were noted in the water maze acquisition test, in which Al-treated Tg2576 mice showed more difficulties in learning the task than Al-exposed wild mice. No significant effects of melatonin in the acquisition task were observed. The present results indicate that Tg2576 mice are sensitive to high dietary Al levels. A significant protector role of melatonin on Al-induced behavioral effects was not observed.