Rabbit and human corneas were mounted in a specular microscope and perfused with a balanced salt solution of varying osmolality (200 to 500 mOsm). Measurements of corneal thickness were made throughout the perfusion period, and at selected times the corneas were fixed and prepared for scanning and transmission electron microscopy. A hypo-osmotic perfusion medium caused an increase in corneal thickness; by comparison, a hyperosmotic perfusion medium decreased corneal thickness in both rabbit and human corneas. Despite the marked changes in corneal thickness and the water movement that occurred across the endothelium, the cellular ultrastructure remained intact. In reversal studies (return to 300-mOsm perfusion medium), corneal thickness returned to control values with no marked changes in endothelial cell structure. These data indicate that the corneal endotheium can tolerate a wide range of solution osmolalities (200 to 400 mOsm) without marked endotheial cell breakdown if the essential ions are present.