Functional Fc receptors have been described in the central nervous system (CNS) in the subependymal periventricular regions, leptomeninges, including brain perivascular tissues, and choroid plexus. The distribution of this receptor activity suggests a role in protection of adjacent nervous tissue from IgG-opsonized antigens, including microorganisms. In this report, we have utilized monoclonal antibodies to human Fc gamma RI, II, and III; 32, IV.3, and 3G8, respectively, to immunohistochemically examine the distribution of these receptors in the CNS. Fc gamma RI was only occasionally present in the CNS where it was identified most often in the choroid plexus. Fc gamma RII was the predominant receptor in brain. It as consistently present in leptomeninges, including brain perivascular regions, arachnoid granulations, and choroid plexus stroma. Some samples of subependymal periventricular tissue also displayed Fc gamma RII. Fc gamma RIII was only identified in subependymal periventricular tissue but not in choroid plexus and arachnoid. These results demonstrate that regions of normal adult brain which produce cerebral spinal fluid (CSF) and border on CSF and vascular compartments display Fc gamma R heterogeneity consistent with that of blood monocytes and systemic macrophages.