Diffusely adherent (DA) Escherichia coli, a newly described category, has been associated with diarrhea in children in some but not all epidemiologic studies. To investigate its diarrheagenic potential, two strains of DA E. coli were fed to adult volunteers in doses of 10(5)-10(10) colony-forming units. None of 22 volunteers who received strain 57-1 or of 21 who received strain C1845 developed symptoms of diarrhea as defined for this study. All volunteers shed the challenge DA E. coli in their stools. Duodenal string cultures were positive in some volunteers only at the highest doses. Only 6 developed IgG or IgA antibodies to whole DA E. coli. Thus, the pathogenic potential of DA E. coli could not be shown in this model. Further studies are needed to characterize potential virulence factors of DA E. coli that might distinguish a pathogenic subset.