Macrophage colony stimulating factor (M-CSF) and its receptor are upregulated in the brain in Alzheimer's disease. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. Amyloid beta (Abeta) immunization experiments suggest that microglia have the capacity to aggressively clear Abeta from the brain under certain circumstances. We examined the role of M-CSF in phagocytosis of fluorescent microspheres and Abeta by cultured microglia. M-CSF treatment increased microglial cell phagocytosis of both microspheres and of Abeta. Antibody neutralization of M-CSF inhibited Abeta uptake induced by overexpression of the M-CSF receptor on microglia. These results suggest that M-CSF could be important in promoting microglial clearance of abnormal protein aggregates such as Abeta.