The use of silicone oil as a retinal tamponade in the treatment of proliferative vitreoretinopathy is often complicated by membrane reproliferation. We studied the development of traction retinal detachments following the intravitreal injection of 15,000 retinal pigment epithelial cells in silicone-, perfluoropropane-, and fluid-filled rabbit eyes. By 28 days a higher proportion of silicone-filled eyes (83%) had severe proliferative vitreoretinopathy than either the perfluoropropane-filled (30%) or fluid-filled (10%) eyes. An in vitro proliferation assay using the vitreous samples showed that the silicone-filled vitreous had increased mitogenic activity for retinal pigment epithelial cells compared with the gas-filled or fluid-filled vitreous. Silicone oil appears to increase proliferation by stimulating the release of more or different mitogenic factors as well as by concentrating active factors into a smaller volume near the retina.