Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.