Using mAbs and immunocytochemistry we have examined the response of macrophages (M phi) after crush injury to the sciatic or optic nerve in the mouse and rat. We have established that large numbers of M phi enter peripheral nerves containing degenerating axons; the M phi are localized to the portion containing damaged axons, and they phagocytose myelin. The period of recruitment of the M phi in the peripheral nerve is before and during the period of maximal proliferation of the Schwann cells. In contrast, the degenerating optic nerve attracts few M phi, and the removal of myelin is much slower. These results show the clearly different responses of M phi to damage in the central and peripheral nervous systems, and suggest that M phi may be an important component of subsequent repair as well as myelin degradation.