Hybridoma anti-DNA antibodies produced by clones derived from fusions of spleen cells from unimmunized MRL/l mice with BALB/c plasmacytomas were examined for their binding to nucleic acid antigens and for their reactivities with anti-idiotype antibodies. All the antibodies bound to a variety of nucleic acids and polynucleotides. This finding suggests that epitopes shared by nucleic acid antigens can account for some of the serologic diversity in lupus serum. Each hybridoma autoantibody had a unique pattern of reactivity with nuclei acid antigens, yet cross-reactions among some of them were found by analyses with anti-idiotype antibodies. These cross-reactions were due to similarities in the antigen-binding regions of the autoantibodies because anti-idiotype Ig blocked the binding of the hybridoma antibody DNA; moreover, polynucleotides inhibited the idiotype anti-idiotype reaction. Cross-reactive idiotypes were found not only among hybridoma anti-DNA antibodies produced by clones derived from the same MRL/l mice but also among antibodies produced by clones derived from different MRL/l mice. The latter finding suggests that families of germ line genes may encode some autoantibodies against DNA.