Various autoantibodies are found in systemic lupus erythematosus. Anti-double-stranded DNA antibodies are the most pathognomonic and among the most extensively studied. Genetic studies of these antibodies and their idiotypes suggest that high-affinity IgG anti-double-stranded DNA antibodies are produced by a process of somatic mutation and clonal expansion favoring sequences with accumulated positively charged amino acids in the complementarity-determining regions. The antigens that trigger this process are not known, but recent studies have suggested that a DNA-protein complex may be implicated. At the tissue level, these antibodies may react directly with membrane proteins or indirectly via complexes with DNA, histones, and heparan sulfate. Serologic studies have sought to establish links between clinical features and the presence of particular non-DNA-binding autoantibodies. Of particular interest have been antibodies to proteins with nucleic acid-binding potential, such as Sm, SS-A (Ro), and SS-B (La).