Abstract In an immunohistochemical study using monoclonal antibodies, which exclusively recognizecells of the monocyte-macrophage lineage, and monoclonal antibodies against the Ia-antigen, we describe the occurrence of macrophages in the developing and adult central nervous system (CNS). In normal adult brain, no macrophages could be detected in the CNS parenchyma; only inthe meninges and the choroid plexes were a few macrophages found. During ontogeny, numerous phagocytic cells infiltrated the CNS parenchyma; these cellswhich did not express Ia are blood-borne. About three weeks after birth, all macrophages had disappeared from the CNS. As microglia in adult and developing brain do not stain with the anti-macrophage antibodies, we suggest that microglial cells are not related to the mononuclear phagocyte system and do not have a hematogenous origin.