Abstract Aluminum, a known neurotoxic substance and a ground-water pollutant, is a possible contributing factor in various nervous disorders including Alzheimers disease. It has been hypothesized that cytokines are involved in aluminum neurotoxicity. We investigated the alterations in mRNA expression of tumor necrosis factor (TNF), interleukin-1 (IL-1), and interferon (IFN), cytokines related to neuronal damage, in cerebrum and peripheral immune cells of mice after exposure to aluminum through drinking water. Groups of male BALB/c mice were administered aluminum ammonium sulfate in drinking water ad libitum at 0, 5, 25, and 125ppm aluminum for 1month. An additional group received 250ppm ammonium as ammonium sulfate. After treatment, the cerebrum, splenic macrophages and lymphocytes were collected. The expression of TNF mRNA in cerebrum was significantly increased among aluminum-treated groups compared with the control, in a dose-dependent manner. Other cytokines did not show any aluminum-related effects. In peripheral cells, there were no significant differences of cytokine mRNA expressions among treatment groups. Increased expression of TNF mRNA by aluminum in cerebrum may reflect activation of microglia, a major source of TNF in this brain region. Because the aluminum- induced alteration in cytokine message occurred at aluminum concentrations similar to those noted incontaminated water, these results may be relevant in considering the risk of aluminum neurotoxicity in drinking water.