Previously, we showed that the Shiga toxin type 2 (Stx2)-expressing Escherichia coli O157:H7 strain 86-24 colonized mice better than did its isogenic stx₂ negative mutant. Here, we confirmed that finding by demonstrating that Stx2 given orally to mice increased the levels of the 86-24 stx₂ mutant shed in feces. Then we assessed the impact of Stx2-neutralizing antibodies, administered passively or generated by immunization with an Stx2 toxoid, on E. coli O157:H7 colonization of mice. We found that such antibodies reduced the E. coli O157:H7 burden in infected mice and, as anticipated, also protected them from weight loss and death.