The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.