Single IgA‐ or IgM‐secreting plasma cells were isolated from histological sections of human jejunum and terminal ileum, and Ig heavy chain variable (V_H ) region genes were amplified and sequenced. Taken together, 62 of 63 cells analyzed harbored somatically mutated V_H region genes, indicating that the vast majority of both IgA‐ and IgM‐secreting intestinal plasma cells derive from germinal center B cells. On average, rearranged V_H genes of IgA‐ and IgM‐secreting plasma cells showed a mutation frequency of 9.0 % and 8.5 %, respectively, which exceeds the level of somatic mutation of V region genes carried by human memory B cells. Moreover, we detected deletions or insertions in the complementarity‐determining regions of 5 of the 58 functional V_H region genes analyzed, suggesting that these alterations may contribute to the diversification of the human antibody repertoire in the course of an immune reaction.