Three mouse strains were assessed for their susceptibility to intestinal colonization by a strain of the enteric bacterial pathogen Escherichia coli O157:H7. Following intragastric inoculation of E. coli O157:H7, the intestines of young adult female CD1, BALB/c, and C57BL/6 mice became colonized, as evidenced by faecal shedding of the pathogen for periods of up to 5 weeks. None of the three mouse strains examined developed overt disease in response to colonization by the organism. Following clearance of the primary inoculum, BALB/c mice, but not CD1 or C57BL/6 mice, appeared to acquire enhanced resistance to recolonization by E. coli O157:H7, as evidenced by a decreased faecal shedding period. This enhanced resistance correlated with the presence and persistence of immunoglobulin A, but not immunoglobulin G, in the serum and faeces directed against the O157 antigen. The implications of these findings to vaccine development against E. coli O157:H7 are discussed.