Chlorhexidine digluconate, a soft contact lens disinfectant, was perfused over rabbit corneal peithelial and endothelial surfaces under a variety of concentrations and conditions. Without protein in the bathing solutions, the cornea swelled when chlorhexidine concentrations of 20 microgram/mL or greater were perfused over the endothelium. Scanning electron microscopy demonstrated rounded, swollen cells with loss of microvilli. Perfusion of the epithelium with chlorhexidine in protein-free Ringer's solution resulted in a dose-dependent sloughing of cells and loss of microvilli, which resulted in little or no swelling when the endothelium was concomitantly bathed with oil. Corneal swelling followed at concentrations of 500 and 1,000 microgram/mL when both corneal surfaces were bathed with protein-free Ringer's solution and the epithelium was perfused with chlorhexidine. With protein included in the bathing solution, no swelling occurred when separate chlorhexidine (500 microgram/mL) and albumin (1%) solutions were applied simultaneously to the epithelial surface of corneas, with the endothelial surface bathed in Ringer's solution.