Abstract The lack of professional afferent APCs in naive brain parenchyma contributes to the systemic immune ignorance to Ags localized exclusively within the brain. Dendritic cells (DCs) appear within the brain as a consequence of inflammation, but no molecular mechanisms accounting for this influx have been described. In this study we demonstrate that Fms-like tyrosine kinase 3 ligand (Flt3L) recruits plasmacytoid DCs (pDCs; >50-fold; p < 0.001) to the brain parenchyma. These pDCs expressed IFN-α, the hallmark cytokine produced by pDCs, indicating recruitment and activation in situ of bona fide pDCs within the brain parenchyma. Flt3L did not increase the numbers of conventional DCs, macrophages, or B, T, NK, NKT, or microglial cells within the brain. Our data demonstrate that Flt3L reconstitutes a crucial afferent component of the immune response, namely, professional APCs within the brain parenchyma, and this could counteract the intrinsic systemic immune ignorance to Ags localized exclusively within the brain.