Highly specific serum autoantibodies directed at cellular macromolecules are detectable in the serum of many patients with autoimmune connective tissue diseases. This phenomenon has been useful in diagnosis and in identifying disease subsets. The mechanism whereby the immune system selects these specific targets, and their relation to the events of disease pathogenesis, remains unclear. The use of monoclonal autoantibodies has increased our knowledge of the molecular associations and components of the often complex heteropolymeric antigenic particles. The advent of antigen cDNA cloning now heralds the next stage in resolution of this understanding with the complete primary structure of the component proteins.