Two cases of Acanthamoeba keratitis and infectious crystalline keratopathy, occurring simultaneously, are presented. Three and 12 months after initiating topical corticosteroid therapy in cases 1 and 2, respectively, alpha-hemolytic Streptococcus viridans was cultured from each cornea. Topical corticosteroid therapy was initiated for the treatment of an annular stromal opacity, presumably secondary to herpes simplex keratitis. Acanthamoeba was identified in culture following penetrating keratoplasty in case 1, and Acanthamoeba polyphaga, Acanthamoeba rhysodes, and Acanthamoeba castellanii were identified using indirect fluorescent antibody staining in case 2. Histopathologic examination and electron microscopy demonstrated sheets of cocci within stromal lamellae characteristic of infectious crystalline keratopathy and double-walled encysted organisms typical of Acanthamoeba. These case reports alert one to the possibility of developing bacterial keratitis, such as infectious crystalline keratopathy, following the use of topical corticosteroids for the treatment of Acanthamoeba keratitis.