We examined a 56-year-old man with keratoconjunctivitis sicca and marked ocular surface disease in whom the prolonged frequent use of topical medications containing the preservative benzalkonium chloride was associated with corneal endothelial damage requiring corneal transplantation in one eye. The histopathologic findings on examination of the excised button were consistent with toxic endothelial disease. Postoperatively, the patient's symptoms continued until the preservative-containing medications were substituted with nonpreserved saline eyedrops.