Microglia are myeloid-lineage inflammatory cells that activate innate and adaptive immune responses within the central nervous system (CNS). They also have important roles in CNS development and homeostasis and can modulate the course of a variety of CNS diseases. We report here the sequential differentiation of murine induced pluripotent stem cells (iPSC) into hematopoietic progenitor-like cells and then into cells with a phenotype and gene expression profile resembling that of primary brain-isolated microglia. Functionally, the iPSC-derived microglia (iPS-MG) produce inflammatory cytokines and reactive oxygen species, demonstrate phagocytic activity and migrate to areas of pathology within the brain following intracranial injection. The ability to readily generate iPS-MG in vitro will facilitate the study of normal and disease-specific microglia and be useful for the development of microglia-based treatments for CNS diseases. Overall design: 21 human samples: 3 "NCRM-5" samples representing an iPS cell line established from cord-blood CD34+ cells (available at NIH CRM); 3 "iMG (NCRM-5)" samples representing microglia derived from the "NCRM-5" iPS cell line; 3 "iNC-012" samples representing an iPS cell line established from peripheral blood hematopoietic progenitor CD34+ cells (made available by Dr. Harry L. Malech lab at NIAID, NIH); 3 "iMG (iNC-012)" samples representing microglia derived from the "iNC-012" iPS cell line; 3 "fMG" samples representing fetal microglia (available from Clonexpress); 3 "DC" samples representing dendritic cells (available from AllCells); and 3 "Mac" samples representing bone marrow macrophages (also obtained from AllCells).