AbstractAmyotrophic lateral sclerosis (ALS) is associated with increased numbers of microglia within the CNS. However, it is unclear to what extent bone marrow (BM)‐derived cells contribute to this microgliosis. We have studied the adoptive transfer of green fluorescent protein (GFP)‐labeled whole BM cells and BM from mice that express GFP only in CX3CR1+ cells (CX3CR1+/GFP) into the CNS of a murine model of ALS having over‐expression of mutant superoxide dismutase (mSOD), and wt littermates. We find that most GFP+ and CX3CR1+/GFP cells are found adjacent to the microvasculature within the CNS, both in mSOD and wt mice. GFP+ and CX3CR1+/GFP cells within the CNS have a variety of morphologies, including cells with an elongated appearance, weak Iba‐1 immunoreactivity, and often mannose receptor immunoreactivity, indicating that these cells are perivascular microglia. Typically, less than 10% of BM‐derived cells had a stellate‐shape and expressed strong Iba‐1 immunoreactivity, as expected for parenchymal microglia, indicating that BM‐derived cells uncommonly generate parenchymal microglia. Adoptive transfer of BM‐derived cells from CX3CR1+/GFP mice revealed that many elongated cells are GFP+, demonstrating that some perivascular cells are derived from BM cells of the CX3CR1+ lineage. The significantly greater numbers of BM cells in mSOD than in control mice indicate that the presence of these BM cells in the spinal cord is regulated by conditioning stimuli that may include irradiation and inflammatory factors within the CNS. © 2009 Wiley‐Liss, Inc.