We compared, retrospectively, the effects of infection in jejunal mucosa with the protozoa cryptosporidia or microsporidia and with the human immunodeficiency virus (HIV) upon mucosal structure and absorptive function in 29 AIDS patients. The presence or absence of protozoal infection was confirmed by transmission electron microscopy. Villus blunting and crypt hyperplasia were seen mainly in the parasite-infected groups, although two patients without parasites also had shortened villi. Absorptive functions, including disaccharidase-specific activities and D-xylose absorption, closely paralleled the degree of small intestinal alteration. Evidence of HIV-infected cells in jejunal mucosa was examined by RNA in situ hybridization and by antigen-capture ELISA of mucosal homogenates. We found evidence of HIV in almost half the patients, which did not correlate with intestinal injury or diminished absorption.