To determine by immunocytochemical analysis of epiretinal membranes whether vascular endothelial growth factor and the fibroblast growth factor FGF-5 are present in patients with proliferative diabetic retinopathy or proliferative vitreoretinopathy. Human surgical specimens of epiretinal membranes were obtained from 11 eyes with proliferative diabetic retinopathy and five eyes with proliferative vitreoretinopathy. Sections were immunostained with an affinity-purified antibody against an internal sequence of human FGF-5 and with a commercially available affinity-purified antibody corresponding to the first 20 residues of human vascular endothelial growth factor. Slides were visualized using avidin-biotin-peroxidase complex. Control studies were performed with nonimmune immunoglobulin G and preabsorbed vascular endothelial growth factor and FGF-5 antibody, respectively. Immunoreactive FGF-5 is present in most cells, including endothelial cells of vascular and avascular epiretinal membranes, but seems to be absent from the extracellular matrix. A similar staining pattern was observed for vascular endothelial growth factor. Vascular endothelial growth factor and FGF-5 are remarkably colocalized in both vascular and avascular epiretinal membranes arising from proliferative diabetic retinopathy and proliferative vitreoretinopathy, respectively. This result questions the concept that the presence of a single angiogenic factor determines the vascular status of an epiretinal proliferation.