Administration of 2,4,6-trinitrophenylated E. coli lipopolysaccharide (TNP-LPS) complexed with mouse IgG antibody to TNP specifically gave rise to a marked production of rheumatoid-like factors (RF) in the recipient mice, in contrast to the low and nonspecific RF production via polyclonal B cell activation by the same dosage of LPS or TNP-LPS alone. The RF activity induced by the LPS immune complexes was associated with both IgG and IgM and directed primarily to the C gamma 2 region as judged by the heterophilic reactivity toward fragments of rabbit IgG. The results suggest that antibody molecules attached to LPS constitute novel epitopic groups on the mitogenic carrier and stimulate B cells in a specific manner to induce the autoantibodies.