The reason a cell leaves the corneal epithelial surface at a particular time is not understood. It is likely that a cell must depend on metabolic energy to accomplish this task successfully and with minimal disruption to the epithelial surface and barrier. The hypothesis under test is that the epithelium is directly dependent on atmospheric oxygen to maintain a normal cell shedding rate. Rabbit corneas were excised in pairs and the surfaces bathed with appropriate media for 400 minutes at 304 mOsm/kg and pH 7.4. The epithelial surface of one cornea was bathed with a normoxic solution as a control, while the other cornea was anoxic. Solutions were collected from the epithelial surface at 50 minute intervals. Cell counts of shed corneal epithelial cells were made by staining with acridine orange and viewing with fluorescence microscopy. Stromal thickness was measured at the beginning and at 400 minutes to confirm hypoxia. The results show that hypoxia does reduce the rate at which cells are shed, at least for collections made during the first 50 minutes (P < 0.01). However, by 150 minutes there was no difference between the hypoxic cornea and the control. This result suggests that cell shedding is dependent on oxygen only during the early part of a period of hypoxia. When the hypoxia is prolonged, other mechanisms intervene which preserve the normal shedding rate.