Naturally occurring antibodies directed against the principal component of the gene are conceptually remarkable as well as of great interest to both basic and applied immunologists. In this article, some of the important literature concerning these antibodies are reviewed, concentrating on studies performed during the last 5 years. One of the major recent advances has been the generation of monoclonal anti-DNA antibodies, studies of which have shed light on the ligand-binding characteristics, idiotypic properties, and genetic origin of anti-DNA and other autoantibodies. The major current hypotheses for the origin of autoantibodies and, in particular, present evidence that anti-DNA antibodies are part of the normal immune repertoire are also discussed. Finally, the evidence that certain subgroups of anti-DNA antibodies may be pathogenic is examined.