Antibodies to exogenous antigen and to self antigen--that is, autoantibodies, are both encoded by the combining of V, D, and J genetic elements in the heavy chain, and V and J in the light chain immunoglobulins. The mechanism which generates autoantibodies does not seem to differ from that which generates the immune response to foreign antigen, and analysis of DNA from normal and autoimmune strains of mice appears similar with no appreciable defects in the immunoglobulin germline genes. Although there is restricted use of particular gene families in murine antibodies to exogenous antigen, the preferential use of particular V genes in murine autoantibodies remains controversial. Until recently, because of the obvious limitations on human experimentation, there was little information about the genetics of the human autoimmune response. Recent developments in molecular cloning techniques, however, some of which are discussed here, have shown that the germline arrangement of the human immunoglobulin variable genes differs from that found in the mouse. Furthermore, there is increasing evidence that human autoantibodies make restricted use of the V gene repertoire, and this indicates that the human autoimmune response is less polymorphic than the murine autoimmune response.