To determine the efficacy and safety of albendazole for treatment of intestinal microsporidosis due to Enterocytozoon bieneusi, 29 patients with AIDS were studied. All had chronic diarrhea, weight loss, and evidence of malabsorption. After 1 month of treatment with albendazole (400 mg orally twice a day), the mean number of bowel movements decreased from 7.0 to 3.8 stools/day (P < .0001) and the mean weight gain was 0.56 kg (P = .259). Albendazole at this dose did not clear E. bieneusi on follow-up small-bowel biopsies, but ultrastructural studies revealed an apparent decrease in parasite burden in 2 patients and an increased proportion of dividing plasmodia in 5 patients. There were no significant adverse events associated with this dose of albendazole. A formal double-blind placebo-controlled study using higher doses has recently been approved and will soon be underway (AIDS Clinical Trial Group protocol 207).