Antibodies to DNA occur prominently in systemic lupus erythematosus and play a central role in pathogenesis. Recent studies on the production of anti-DNA antibodies in both mouse and man suggest that this response can result from a variety of immunoregulatory disturbances of B and/or T cells. The immunogenic role of DNA as opposed to other self or foreign antigens remains unclear, however. Future studies will delineate the structure of anti-DNA antibodies and thereby determine the role of antigen drive in this response.