A longitudinal analysis of 12 lupus patients has been undertaken to assess their autoantibody reactivity by ELISA with histones, Sm-D peptides, ubiquitin and DNA. As controls patients with rheumatoid arthritis and tuberculosis were studied. Whereas the control groups showed little evidence of autoantibody reactivity 25% or more of the lupus patients had raised levels of autoantibodies against eight of the nine antigens tested. Of particular note was the fact that approximately 70% of the blood tested possessed antibodies reacting with Sm-D peptide 1-20. In contrast only one patient had anti-Sm antibodies by counter immunoelectrophoresis. In general the levels of antibodies to core histones reflected disease activity unlike the levels of anti-H1 antibodies. High levels of antibodies to ubiquitin often seemed to correlate inversely with active lupus and DNA antibody levels.