Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg2+-ATPases located in the endoplasmic reticulum and plasma membranes. We studied the effects of aluminum on calcium transport in the adult rat brain. We examined 4'Ca-uptake in microsomes and Ca2+-ATPase activity in microsomes and synaptosomes isolated from the frontal cortex and cerebellum of adult male Long-Evans rats. A ndependent 45Ca-uptake was similar in microsomes from both brain regions. The addition of 50-800 y M AICI, resulted in a concentration-dependent inhibition of 45Ca-uptake. Mg2+-dependent Ca2+-ATPase activity was significantly lower in synaptosomes compared to microsomes in both frontal cortex and cerebellum. In contrast to the uptake studies, A1C13 stimulated Mg2+-dependent Ca2+-ATPase activity in both microsomes and synaptosomes from both brain regions. To determine the relationship between aluminum and Mg2+, we measured ATPase activity in the presence of increasing concentrations of Mg" or AlCl,. Maximal ATPase activity was obtained between 3 and 6 mM Mg2*. When we substituted AlCl, for Mg2+, AT-Pase activity was also stimulated in a concentration-dependent manner, but to a greater extent than with Mg2+. One interpretation of these data is that aluminum acts at multiple sites to displace both Mg" and Caz+, increasing the activity of the Ca2+-ATPase, but disrupting transport of calcium.