To evaluate pluronic polyol F-127 (PF-127) as a vitreous substitute and an intraocular drug delivery system, a total vitrectomy was performed on 18 New Zealand rabbits (18 eyes). The vitreous was replaced with either PF-127 (9 eyes) or balanced salt solution (9 eyes). There was little difference clinically between the eyes containing PF-127 and the control eyes. Both groups showed mild postoperative inflammation, with no differences in intraocular pressures. Histopathologic findings for the control group showed no significant retinal alteration, and serial ERG findings were within normal limits. In contrast, the eyes containing PF-127 showed marked destruction of the retina by 2 weeks after surgery. The ERG amplitudes decreased dramatically to a flat tracing by 24 hours after surgery. Although it is attractive as a potential vitreous substitute, PF-127 is not safe for human use, at least at the concentration used. RETINA 10:297–300, 1990