A 67-year-old man had a diagnosis of dapsone-resistant lepromatous leprosy. He received clofazimine (Lamprene) at a dosage of 100 mg twice daily. After 3 years of therapy, results of slit-lamp examination disclosed myriad polychromatic crystals diffusely involving the cornea and perilimbal conjunctiva of both eyes. Thick sections (1 micron) from a conjunctival biopsy showed numerous rectangular-to-rhomboidal crystals within stromal fibroblasts and macrophages. By electron microscopy, these cells contained elongated, membrane-bound, cleft-like spaces that corresponded to the sites where crystals had been present previously. Additionally, complex lipid inclusions were observed in mesenchymal cells as well as in endothelial cells and pericytes of blood vessels. The ocular side effects of clofazimine therapy are reviewed. Clofazimine-induced keratopathy should be included in the differential diagnosis of patients with polychromatic crystalline deposits in the corneas. To the best of the authors' knowledge, this complication of clofazimine therapy has not been described previously.