A 30-year-old homosexual man with a positive serologic test for human immunodeficiency virus and a history of successfully treated disseminated cutaneous sporotrichosis developed a granulomatous uveitis that worsened with topical and subconjunctival steroid therapy. Culture of the aqueous aspirate yielded Sporothrix schenckii. The patient was treated with intravenous amphotericin B and intravitreal amphotericin B, kanamycin sulfate, and amikacin sulfate. Subsequent aqueous and vitreous cultures were negative, but the intraocular inflammatory process progressed and ultimately led to enucleation of the eye. Histopathologic examination revealed granulomatous inflammation of the anterior uvea and scattered S schenckii in the anterior and posterior chambers. Electron microscopy demonstrated that most of the organisms had disorganized protoplasm. Although treatment failed to ameliorate the progressive intraocular inflammatory process, the negative cultures and the electron microscopic observations suggest that the treatment was reasonably effective in killing S schenckii within the eye. To our knowledge, this is the first case report of S schenckii endophthalmitis in a patient with human immunodeficiency virus infection.