AbstractWe have analyzed by the limiting dilution assay on spleen cells from (NZB × NZW)F1 hybrid mice the repertoire of lipopolysaccharide‐responsive murine χ‐ and λ1‐secreting B cells committed to the production of anti‐DNA autoantibodies to determine the contribution of the heavy and light chains to anti‐DNA specificities. Our results demonstrated that anti‐DNA precursors were predominantly found in the χ‐secreting B cell population, but not in λ‐secreting B cells, while anti‐hapten, dinitrophenyl, and anti‐tetanus toxoid activities were distributed fairly well in both populations of B cells. This suggests that the Vχgene segments are critically involved in the generation of anti‐DNA specificities, and that at least at the germ‐line gene level, the heavy chain V region genes by themselves are not able to confer the anti‐DNA autoreactivity.