Iron is necessary for normal neural function but it must be stringently regulated to avoid iron-induced oxidative injury. The regulation of systemic iron is through the proteins transferrin (iron mobilization) and ferritin (iron sequestration). This study examines the cellular and regional distribution of iron and the iron-related proteins ferritin and transferrin in selected regions of the adult and aged rat brain. This information is a necessary prerequisite to understanding the mechanism by which iron homeostasis is maintained in the brain. The predominant cell type containing ferritin, transferrin, and iron throughout the brain at all ages is the oligodendrocyte. Neurons in most brain regions contain granular iron deposits which become more apparent with age. Ferritin and iron are also present in microglial cells in all brain regions, but are particularly abundant in the hippocampus. These latter cells visibly increase in number in all brain regions as the animal approaches senescence. Another area in which immunostaining is notable is surrounding the III ventricle, where transferrin is found in the choroid plexus and ependyma and ferritin and iron are present in tanycytes. The results of this study indicate an important role for neuroglia in the regulation of iron in the brain and also implies that a transport system may exist for the transfer of iron between the brain and cerebrospinal fluid. In the normal rodent brain, the principal cell of iron regulation is the oligodendrocyte; however, the role of microglial cells in the sequestration and detoxification of iron may be significant, particularly as the animal ages. With age there is an increase in stainable iron in neurons without a concomitant increase in neuronal ferritin immunostaining, suggesting a ferritin independent accumulation of neuronal iron with age.