The proposed research project focuses on studies designed to elucidate basic causal mechanisms in systemic lupus erythematosus and related disorders. By the application of recently devised techniques based on advances in nucleic acid chemistry and molecular biology, a detailed analysis of circulating DNA in both normal individuals and SLE patients is proposed. This analysis is designed to elucidate basic causal mechanisms including possible causal involvement of microorganisms in these diseases. The use of recombinant DNA methodology will allow this work to be greatly faciliated over that previously carried out in this laboratory. Other studies relevant to the role of extranuclear DNA and antibodies to it will also be pursued as will studies designed to identify putative causative microorganisms in these diseases.