Transcorneal freezing was used to destroy the central 10, 50, or 90 percent of the endothelium in rabbit and cat cornea. The regenerative process was studied in each species by pachometry, electron microscopy, and autoradiographic analysis of the incorporation of tritiated thymidine into nuclear DNA. In rabbit, extensive cellular division occurred at the margin of the wound; in most cases an endothelial monolayer made up of cells of normal size and morphology was re-established by 10 days, and corneal thickness returned to near normal in 4 to 30 days (depending on the extent of the original injury). Junctional complexes and extensive implication of lateral cell borders were present in the endothelium of rabbit corneas that had returned to normal thickness. By contrast, in cat, little cell division occurred and regenerative activity consisted of enlargement and migration of the cells at the margin of the wound. An intact monolayer was eventually formed, but the endothelial cells in central cornea remained enlarged and irregular in size and shape even after 1 month. Junctional complexes were rarely seen between these cells and they did not overlap normally. Corneal thickness remained elevated after 1 month in cat corneas in which 50 and 90 percent of the cells had been destroyed. These results suggest thai the regenerative capacity of the corneal endothelium in cat is more analogous to that of man. Cat will therefore provide a practical model for future studies of the effects of new intraocular surgical procedures, drugs, or devices on a" stressed" corneal endothelium.