Aluminum (Al) has been said to associate with the Alzheimer's-like neurodegeneration in humans. One of the proposed mechanisms for the action of Al is that excess Al might interfere with trace metal metabolism. In this study, the levels of Ca, Mg, Cu, and Zn in blood, liver, and different regions of the brain (separated into the cortex, hippocampus, cerebellum, and brainstem) were measured in mice after daily oral administration of AlCl (100 mg/kg body weight) for 2 mo. It was found that upon prolonged oral admin3 istration of Al, serum Al level was elevated significantly. There was no marked change in serum Ca, Mg, Zn, or Cu content. In the liver, Al content was not increased but there was a significant elevation in Cu and Zn content compared to control animals, probably due to the prolonged administration of the acidic salt solution. In brain, there was a significant twofold increase in Al in the hippocampus and a significant decrease in Al in the cortex. In addition to regional changes in Al content, Zn content in the hippocampus and increased Cu content in the hippocampus, cortex, and brainstem were significantly reduced. Data demonstrated that Al could alter Zn and Cu homeostasis in selected brain regions. The possible relation between Al and neuronal cell injury was discussed.