Perfluorotributylamine, a liquid fluorochemical used in artificial blood substitution, was evaluated for potential application as a vitreous substitute having heavier density than saline. It was injected into the vitreous of 38 rabbit eyes after mechanical vitrectomy or gas compression of the vitreous with perfluoropropane. The eyes were observed for periods of up to five months. Clinically the liquid occupied the lower vitreous space but gradually dispersed into smaller fluorochemical droplets. In the upper vitreous clusters of cells appeared within three to four weeks which precipitated on the posterior lens surface and in the cortical vitreous. In eyes with experimental retinal detachment perfluorotributylamine had physical properties which provided mechanical retinal tamponade. Its interfacial tension prevented passage through iatrogenic retinal breaks. Histopathologic findings showed irregularly shaped defects in the outer segment disks as early as two days after vitreous replacement. These changes appeared to reverse if perfluorotributylamine was removed after two days. The cellular response in the vitreous consisted primarily of monocyte-derived macrophages capable of ingesting fluorochemical (foam cells).