Abstract The meningeal and perivascular spaces of the central nervous system (CNS) are inhabited by specialized macrophages. Under steady state conditions, we discovered two populations: immature macrophages (MHC-II−) and mature macrophages (MHC-II+). Microarray analyses revealed that IL-10 and TGFb were upstream regulators of the immature macrophage transcriptome, which included stem cell-specific genes. These data suggest that immature macrophages represent local progenitors maintained by anti-inflammatory cytokines within the meninges. Interestingly, in naïve mice MHC-II+ macrophages were enriched upon aging and upregulated inflammatory genes, suggesting age-based maturation. To better understand the dynamics of these macrophages, we triggered CNS inflammation by inoculating mice with lymphocytic choriomeningitis virus (LCMV). Both myeloid populations were infected by the virus, and intravital imaging studies revealed that they were targeted by infiltrating virus-specific CD8+ T cells, which promoted their depletion. Following viral clearance, myeloid repopulation of the meninges was derived largely from infiltrating monocytes that engrafted this CNS niche and adopted a transcriptomic signature of mature resident meningeal macrophages. In stark contrast, sterile depletion of meningeal macrophages without infection induced massive local proliferation of immature macrophages that transformed into mature macrophages and repopulated the meninges. This occurred in the absence of peripheral monocyte engraftment. Collectively, these data indicate that the CNS meninges are inhabited by two macrophage populations with a differential ability to repopulate the niche based on the inflammatory milieu.