Idiotypes are serologically defined markers in the variable region of an antibody molecule. In the study of autoimmunity, these markers have been valuable probes in defining patterns of autoantibody variable region gene utilization, mechanisms of immune dysregulation, and the operation of the network in the generation of abnormal responses. Recent advances in the molecular analysis of immunoglobulin genes have provided insights into the structural basis of autoantibody idiotypes and the manner in which sequence homologies between idiotype-bearing antibodies and autoantigens can lead to autoreactivity. Immune manipulation using these sequences could lead to novel models of disease as well as prospects for immunotherapy.