Otolaryngologists can play an important role in the care of patients with acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus infection. We present the case of an AIDS patient who was hospitalized for dehydration and who was soon found to have sinusitis and subsequent disseminated infection caused by Acanthamoeba. To treat the Acanthamoeba infection, the patient was started on oral itraconazole and intravenous metronidazole; i.v. pentamidine was added 2 days later. Despite aggressive therapy, on the eleventh day of hospitalization, the patient was obtundent and provided minimal response to noxious stimuli. He died on the sixteenth day of hospitalization. This case is one of only six reported cases of Acanthamoeba associated with sinusitis. Current therapeutic regimens have not been successful for most of these patients, and the prognosis is poor.