The identification of cells comprising epiretinal membranes is difficult because of the phenotypic changes that occur. Examination of intermediate filament protein content by immunocytochemical analysis can help to identify some cells with altered ultrastructure but is not always definitive because altered expression of intermediate filament proteins can also occur. To examine this issue further, the authors utilized a postembedding immunocytochemical technique with epiretinal membranes in which they were able to double label for keratin, a useful marker for identifying retinal pigment epithelial cells, and glial fibrillary acidic protein (GFAP), a useful marker for identifying glial cells. Nine of ten idiopathic epiretinal membranes contained cells that labeled for GFAP and not keratin. Two of these membranes also contained cells that labeled only for keratin and one membrane contained cells that simultaneously labeled for both GFAP and keratin. Other types of epiretinal membranes had an equal participation by cells that expressed only GFAP or keratin (12 of 17 membranes contained cells positive for keratin; 13 of 17 contained cells positive for GFAP). Ten of 17 nonidiopathic membranes contained cells simultaneously expressing GFAP and keratin, although they comprised only a minor subpopulation of the total number of cells present. These findings demonstrate that keratin and GFAP are not mutually exclusive intermediate filament proteins in cells of epiretinal membranes and that, although each may provide a helpful adjunct for cell type identification, neither is an absolutely specific marker.