We have investigated the level of expression of CD4 and MHC-II antigens on CNS cells and compared it to that on monocytes. MHC-II antigens were expressed spontaneously on cultured astrocytes and monocytes, whereas they were detected only after IFN gamma stimulation of microglial cells. In vitro, CD4 receptor was present on monocytes but not on neurons, astrocytes or microglial cells. In normal brain, CD4 antigen was expressed on perivascular microglial cells, a specialized microglia expressing monocytic markers, whereas in HIV1-infected brain, CD4+ cells were numerous and scattered throughout the whole parenchyma. These CD4+ macrophages may be HIV1-infected monocytes which have crossed the blood-brain barrier after infection, or perivascular microglial cells infected by HIV1-infected blood lymphocytes or five virions.