Isospora belli, a coccidian parasite in humans, has been described as causing chronic diarrhea and acalculous cholecystitis in patients with the acquired immunodeficiency syndrome (AIDS). Diagnosis can be made at the tissue level in the epithelium of the small bowel and by fecal examination. Disseminated extraintestinal forms are uncommon. We studied 118 adult patients with AIDS and chronic diarrhea using stool analysis and endoscopy with duodenal biopsy specimen collection. These samples were processed by routine histology and transmission electron microscopy. Isosporosis was diagnosed in 8 cases. In 2 of them, unizoite tissue cysts were present in the lamina propria, with negative results in stool materials. The cysts were located within a large parasitophorous vacuole. There were no structural means of differentiating the species level of Isospora based on morphology using light or electron microscopy. We believe further work should be done to determine if unizoite tissue cysts are part of the cycle of I belli or of other species of Isospora that could be pathogenic in immunocompromised hosts.