Prolonged topical trifluridine treatment of herpes simplex keratitis in three elderly patients produced slightly raised dysplastic corneal epithelial lesions. The involved epithelium had a ground-glass appearance and exhibited opaque cells, edema, and spindle-shaped surface cells. Histopathology demonstrated severe cellular atypism, loss of cell polarity, dyskeratosis, parakeratosis, and a few mitotic figures. The pathological change was apparently intraepithelial. After scraping, the edema and opaque cells in the regenerated epithelium gradually disappeared in 3-4 months on cessation of trifluridine therapy. In one patient recurrence of dendritic keratitis, 5 weeks after scraping, was treated by topical bromovinyldeoxyuridine eye drops. Since severe epithelial dysplasia may represent a precancerous condition, prolonged use of trifluridine should be avoided.