Myelin phagocytosis in Wallerian degeneration of peripheral nerves depends on invasion of nerves by non-resident macrophages. The present study was done to clarify the role of the macrophage complement receptor type 3 (CR3) in myelin removal. Myelin phagocytic capacity of invading macrophages was abolished by treatment of cultured nerves and macrophages with anti-CR3 antibody or by serum complement depletion with cobra venom factor. This indicates that myelin phagocytosis is mediated by the macrophage CR3.