The ability of enterotoxigenic Escherichia coli H10407, which possesses colonization factor antigen I, to colonize the intestinal mucosa of infant mice was considerably better than that of its colonization factor antigen I-negative derivative H10407-P. The latter strain previously was shown to lack cell adhering ability in vitro and to have a diminished capacity to infect human volunteers as compared with the parent strain. D-Mannose blocked both colonization by an enterotoxigenic E. coli isolate (801) possessing both mannose-resistant and mannose-sensitive adhesins and the in vitro adherence of the strain to intestinal segments of infant mice. A derivative of another enterotoxigenic E. coli strain (lacking both mannose-sensitive and mannose-resistant adhesins obtained by in vivo passage showed a significant increase in colonizing ability in comparison with the parent strain. We conclude that the infant mouse model of infection of intestinal mucosa complemented by in vitro adherence assays with excised intestinal tissue is suitable for the study of the bacterial properties responsible for the various stages of intestinal colonization by human enterotoxigenic E. coli.