Dendritic cells (DC), while absent from the normal CNS parenchyma, have been demonstrated in delayed type hypersensitivity (DTH), experimental allergic encephalomyelitis (EAE), and some MS lesions. We demonstrate that an acute excitotoxic lesion results in DC recruitment to the brain, with maximal cells between days 3 and 5. Clodronate liposome-mediated depletion of cerebral perivascular macrophages does not prevent recruitment of DC; however, a lesion in a whole-body irradiated animal does not show evidence of DC recruitment. We conclude that DC are recruited to an excitotoxic lesion from a blood-derived cell population. This may have implications for neuropathologies involving DC recruitment.