In order to determine the origin of brain phagocytes brain slices and optic nerve segments from adult Lewis rats were transplanted into the peritoneal cavity of syngenic recipients. The specimens were contained in Millipore diffusion chambers fitted with membranes of either 0.22 or 5.0 microns pore size. The either blocked or allowed the access of non-resident cells. Each recipient rat received both a 0.22 and 5.0 microns pore chamber. Later (3-16 days), the specimens were recovered and analyzed by monoclonal antibody techniques and electron-microscopy. Endothelia, GFAP+ astrocytes, ED1-/ED2+/RCA-1+/OX-6-perivascular cells and ED1-/ED2-/RCA-1+/lysozyme--microglia were found to have survived the procedure. Cells of the macrophage phenotype (ED1+/ED2+/RCA-1+/lysozyme+/vimentin+ with phagocytic vacuoles), however, were only found in large numbers in specimens kept within 5.0 microns pore size chambers, giving access to non-resident cells, and were exceedingly rare in specimens from 0.22-micron pore chambers. It has been concluded that the majority of brain phagocytes found after lesions do not originate from microglia or perivascular monocytic cells, but rather from invading cells.