Retinal detachments are frequently accompanied by retinal pigment epithelial cell and glial cell proliferation. This may be important in the pathogenesis of proliferative vitreoretinopathy and may also play a role in the failure of some eyes to regain visual function despite anatomically successful retinal reattachment surgery. In this study, we demonstrate that a retina-derived substance or substances stimulates the proliferation of retinal pigment epithelial cells (250% above control) and astrocytes (150% above control) in vitro. The stimulation of proliferation occurs in the absence of serum, but is accentuated by serum. There is some degree of target-cell specificity as there is no stimulation of smooth-muscle-cell proliferation. Morphologic changes induced in the proliferating cell types as well as preliminary characterization suggest that one or more of the previously described eye-derived growth factors may be involved.