We have utilized surgically resected human central nervous system (CNS) tissue to determine the expression and functions of Fc receptors (FcyR) on individual cell types found within the CNS. We observed all three classes of FcyR on microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes. Incubation of cultured microglia with immune complexes (antibody-coated red blood cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and oxidative bursts. We also found that microglia have the capability to produce T cell stimulatory soluble mediators after FcyR crosslinking. These functional responses were enhanced by pretreatment of the microglia with interferon-y (IFN-y). Our results implicate microglial effector responses triggered by interaction of FcyR with opsonized antigens as potential mediators of tissue injury within the CNS. Such injury may be particularly applicable to multiple sclerosis, an inflammatory demyelinating disease characterized by intrathecal production of immunoglobulins and cytokines.