Inflammation is an important neuropathological change in Alzheimer’s disease (AD). However, the pathophysiological factors that initiate and maintain the inflammatory response in AD are unknown. We examined AβPP V717F transgenic mice, which show numerous brain amyloid-β (Aβ) deposits, for expression of the macrophage colony-stimulating factor (M-CSF) and its receptor (M-CSFR). M-CSF is increased in the brain in AD and dramatically augments the effects of Aβ on cultured microglia. AβPP V717F animals 12 months of age showed large numbers of microglia strongly labeled with an M-CSFR antibody near Aβ deposits. M-CSFR mRNA and protein levels were also increased in brain homogenates from AβPP V717F animals. Dystrophic neurites and astroglia showed no M-CSFR labeling in the transgenic animals. A M-CSF antibody decorated neuritic structures near hippocampal Aβ deposits in transgenic animals. M-CSF mRNA was also increased in AβPP V717F animals in comparison with wild-type controls. Simultaneous overexpression of M-CSFR and its ligand in AβPP V717F animals could result in augmentation of Aβ-induced activation of microglia. Because chronic activation of microglia is thought to result in neuronal injury, the M-CSF system may be a potential target for therapeutic intervention in AD.