To elucidate the specific role of somatic hypermutation (SHM) in mucosal immunity, we generated mice carrying a knock-in point mutation in Aicda, which encodes activation-induced cytidine deaminase (AID), an enzyme essential to SHM and class-switch recombination (CSR). These mutant AID^G23S mice had much less SHM but had normal amounts of immunoglobulin in both serum and intestinal secretions. AID^G23S mice developed hyperplasia of germinal center B cells in gut-associated lymphoid tissues, accompanied by expansion of microflora in the small intestine. Moreover, AID^G23S mice had more translocation of Yersinia enterocolitica into mesenteric lymph nodes and were more susceptible than wild-type mice to oral challenge with cholera toxin. Together our results indicate that SHM is critical in maintaining intestinal homeostasis and efficient mucosal defense.