We describe the identification of the protozoan parasite Enterocytozoon bieneusi in the stool of a patient who was not infected with HIV but who presented with persistent diarrheal disease and severe abdominal complaints. The patient was not infected with HIV but had been noted to have a decreased CD4 cell count since at least 1992 and had had a prior episode of cryptococcal meningitis. The organisms were detected in stool smears with a modified trichrome stain and were identified to the species level by transmission electron microscopy of the stool. The patient responded readily and dramatically to treatment with albendazole, with resolution of symptoms and clearance of the organisms from the stool. Eight or possibly nine other cases of E. bieneusi infection associated with diarrheal disease in individuals who were not infected with HIV were identified in the English-language literature. In two individuals with intact immune function, symptoms were self-limited and diarrheal disease resolved within 2 weeks. The cases summarized herein suggest that E. bieneusi may be more commonly associated with sporadic diarrheal disease than was previously suspected and that the immune system may play a role in the control of this organism within the intestine.