A commercial perfluoroether liquid, Fomblin-H Fluorinated Fluid, which is transparent and viscous, was investigated as a possible long-term vitreous substitute. The material belongs to a family of perfluorocarbon derivatives that are generally inert and nontoxic. A space for the vitreous substitute was created in rabbit eyes by a vitreous compression technique using perfluoropropane gas. Fomblin caused gliosis of the retina at 1 month after intravitreous injection. Preretinal membrane formation and retinal disorganization and detachment occurred in two of four eyes enucleated at 3 months, and in all five eyes enucleated at 4 or 6 months. Vacuoles presumably filled with Fomblin were localized histopathologically within the retina. In control eyes injected with medical-grade silicone oil, abnormalities were limited to moderate edema of the nerve fiber and ganglion cell layer. Fomblin was not as well-tolerated by the rabbit retina as was medical-grade silicone oil. Fomblin is not a suitable vitreous substitute.