Low viscosity perfluorocarbon liquids are useful adjuncts during vitreoretinal surgery. This study evaluates perfluoro-n-octane (PFnO) for intraoperative use by examining ocular tolerance in rabbits and pigs. Rabbits were treated with intravitreal placement of PFnO for 48 hours and were examined during a period of 2 months following treatment. No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina were observed. Small residual amounts of PFnO produced no adverse histologic changes 6 months after treatment. In pigs treated with mechanical vitrectomy and placement of PFnO for 3 hours, electron microscopic evaluation of the retina confirmed that the liquid had been well tolerated. These findings indicate that PFnO is safe for intraoperative use. When PFnO remained in the vitreous cavity of rabbits for longer than 1 week, varying degrees of globule dispersion occurred. Furthermore, histologic examination revealed changes in the inferior retina: photoreceptor outer segments were distorted, the outer plexiform layer was narrowed, and preretinal accumulation of macrophages had occurred.