Increased inflammatory activity accompanies normal brain aging. Whereas local glial cell activation, upregulation of cytokines and transcriptional alterations of inflammatory factors are well-documented components of this complex process, it is unclear whether blood-derived leukocytes also contribute to the age-related changes. The present study of normal mouse brain applied single and double immunohistochemistry to reveal for the first time that dendritic cells (DCs) and T-cells are important components of the general increased inflammatory state, which was documented by upregulation of reactive astrocytes and microglia. B-cells and mast cells do not contribute to this inflammatory response. Dendritic cells and T-cells appeared at about 12 months of age and their number increased further during aging. In 24-month-old animals a dense network of DCs interspersed with T-cells pervaded brain areas where substantial histopathological changes and a volumetric decrease have been reported. All CD11c(+)-DCs displayed the typical dendritic shape and expressed the myeloid specific integrin CD11b. Some of the DCs were also CD205- or MIDC8-immunoreactive and expressed the cathepsins S and X. The emergence and prolonged presence of leukocytes might indicate a crucial role of these cells in local, age-related immune responses in the brain.