In this investigation, the role of antibodies against Clostridium difficile toxins A and B in protecting hamsters against C. difficile-associated ileocecitis was examined. We also studied the transfer of protection against C. difficile-associated intestinal disease from immunized female hamsters to their infants. Adult female hamsters immunized parenterally with toxoid A or a mixture containing both toxoids A and B were protected against clindamycin-induced C. difficile-associated fatal ileocecitis. On the other hand, hamsters immunized with toxoid B or a broth filtrate from a nontoxigenic strain of C. difficile were not protected against C. difficile-induced ileocecitis. Antibody against the immunizing toxoid could be demonstrated in both the serum and the cecal contents of hamsters. Some infant hamsters from mothers immunized with toxoid A or AB were protected against C. difficile-associated ileocecitis, while infant hamsters from mothers immunized with toxoid B or a nontoxigenic broth filtrate were not protected against disease. Neutralizing antibodies to toxins A and B could be demonstrated in both maternal milk and serum, as well as in infant serum and intestinal contents. Foster-mothering experiments demonstrated that maternal protection of infants against C. difficile-associated ileocecitis was transferred to infant hamsters through breast milk. These results suggest that toxin A may play a more important role in the pathogenesis of C. difficile-associated ileocecitis in hamsters than toxin B. Furthermore, variations in the severity of C. difficile-associated illness in infants and adults may reflect the lack or presence of passively or actively acquired immunity against C. difficile toxins.