Two of four cases of Mycobacterium fortuitum keratitis occurred after corneal surgery with contact lens wear, one was associated with extended contact lens wear alone, and one occurred after a foreign body injury. All cases were characterized by pain, conjunctival hyperemia, stromal inflammation, and ulceration. Diagnosis was made by culture and acid-fast staining of corneal scrapings. On the basis of published experience with amikacin for the treatment of nonocular M. fortuitum infections, three patients were treated with topical amikacin. Two patients responded clinically, but histopathologic examination of a penetrating keratoplasty specimen in one of the two disclosed persistent infection. One patient was cured of early disease by debridement alone. Rapid diagnosis and absence of corticosteroid use were the two most important determinants of successful therapy. In advanced cases, infection may be cured and useful vision restored by penetrating keratoplasty.