Microglia are immune system cells associated with Alzheimer's disease plaques containing β-amyloid (Aβ). Murine microglia internalize microaggregates of fluorescently labeled or radioiodinated Aβ peptide 1–42. Uptake was confirmed using aggregates of unlabeled Aβ detected by immunofluorescence. Uptake of Aβ was reduced by coincubation with excess acetyl–low density lipoprotein (Ac–LDL) or other scavenger receptor (SR) ligands, and DiI-labeled Ac–LDL uptake by microglia was blocked by excess Aβ. CHO cells transfected with class A or B SRs showed significantly enhanced uptake of Aβ. These results show that microglia express SRs that may play a significant role in the clearance of Aβ plaques. Binding to SRs could activate inflammation responses that contribute to the pathology of Alzheimer's disease.