Since the first reports of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE) in 1957, studies of nucleic acid immunochemistry have grown in two directions. One has been the analysis of the specificity, the nature and the origins of these autoantibodies. The second has been exploration of anti-nucleic acid antibodies that can be induced experimentally, their specificities, and their application as biochemical reagents. Although the properties of autoantibodies and experimentally induced antibodies differ in certain respects, these two lines of research are complementary and provide important information for each other. For example, the production of autoantibodies by adjuvant-stimulated B cells yields a background that has to be considered in evaluating the specificity of weak responses to experimental nucleic acid immunogens: in turn, the possibilities and limitations of experimental immunization should be considered in evaluating possible stimuli for autoantibody production. Several aspects of nucleic acid immunochemistry have been described and evaluated in previous reviews. Following some general statements of historical perspective, this review will emphasize questions addressed and findings of about the last five years.