Under steady-state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c-eYFP mice. We previously showed that these mice carry the Crb1rd8 mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c-eYFP+ cells within the CNS may be due to pathology associated with the Crb1rd8 mutation. We generated CD11c-eYFP Crb1wt/wt mice and compared the distribution and immunophenotype of CD11c-eYFP+ cells in CD11c-eYFP mice with and without the Crb1rd8 mutation. The number and distribution of CD11c-eYFP+ cells in the CNS was similar between CD11c-eYFP Crb1wt/wt and CD11c-eYFP Crb1rd8/rd8 mice. CD11c-eYFP+ cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood-brain barrier. CD11c-eYFP+ cells within the retina and cerebral cortex of CD11c-eYFP Crb1wt/wt mice expressed CD11b, F4/80, CD115 and Iba-1, but not DC or antigen presentation markers, whereas CD11c-eYFP+ cells within the choroid plexus and pia mater expressed CD11c, I-A/I-E, CD80, CD86, CD103, DEC205, CD8alpha and CD135. The immunophenotype of CD11c-eYFP+ cells and microglia within the CNS was similar between CD11c-eYFP Crb1wt/wt and CD11c-eYFP Crb1rd8/rd8 mice; however, CD11c and I-A/I-E expression was significantly increased in CD11c-eYFP Crb1rd8/rd8 mice. This study demonstrates that the overwhelming majority of CNS CD11c-eYFP+ cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016.