Five patients with AIDS had disseminated infection due to Septata intestinalis, a recently described organism. S. intestinalis infection was suspected after detection of spores in stools and urine and confirmed by transmission electron microscopy of duodenal biopsies or of cell culture of urine sediment. Clinical features included chronic diarrhea that was usually associated with fever, cholangitis, sinusitis, bronchitis, or mild bilateral conjunctivitis. Mean CD4 cell count was 22/microL. Patients treated with albendazole (400 mg orally twice a day) for a mean of 19 days had a dramatic and rapid clinical response to therapy. Significant reduction of parasite shedding was also observed during therapy; S. intestinalis was cleared from stools of all patients and from urine of 3. In 2 patients, however, microsporidian spores were detected in feces during follow-up and mild diarrhea recurred. Therefore, albendazole seems to have a significant but transient effect in treatment of S. intestinalis infection.