Specimens obtained from eyes with various ocular diseases were examined immunohistochemically using a panel of monoclonal antibodies (Ki-M1P, K1-M4, CD68, anti-lysozyme, and anti-cytokeratins) to establish the occurrence of macrophages in the retina and periretinal tissues and to determine whether they can be distinguished from migrated cells of the retinal pigment epithelium (RPE). Eyes with proliferative diseases and intraocular melanomas were found to contain more macrophages in the retina than those with uveitis and glaucoma. The epiretinal membranes and subretinal space in eyes of the former group often exhibited additional clustered macrophages and migrated RPE cells. In all specimens studied, RPE cells reacted with antibodies KL-1, CK7, CK18, or CK19 but not with the CD68, Ki-M1P, or lysozyme antibodies. Control eyes without any known disease also contained rare macrophages in the retina. In conclusion, macrophages are regular and normal constituents of the retina that can be clearly distinguished immunohistochemically from migrated RPE cells. Their frequency varies depending on the type of ocular disease involved.