Circulating antibodies to certain nuclear antigens are of diagnostic use and contribute to our ability to determine prognosis in terms of predicting particular organ system involvement in the rheumatic diseases. Examples include antibodies to DNA and to the Sm antigen associated with systemic lupus erythematosus (SLE) (l), antibodies to nuclear ribonucleoprotein n-RNP associated with mixed connective tissue disease (2), and antibodies to another nucleic acidic protein antigen, PM-1, which have a high specificity for polymyositis (3). A recent report of 16 patients who had circulating Sm antibodies suggested that this serologic pattern might be indicative of a more benign form of SLE with nonprogressive nephritis (4). The purpose of the present study was to compare the disease patterns in patients with circulating Sm and DNA antibodies and to determine the relative importance of the presence of Sm antibody or the absence of DNA antibody in the disease which occurred. MATERIALS AND METHODSCalf thymus nuclear extract, extractable nuclear antigen (ENA), and DNA were prepared by previously published techniques (5). The Sm antigen was prepared from the washed DNA-histone fraction of the nuclear extract. The resulting pellet was treated with DNase (Worthington Biochemical Corporation) for one hour at 37OC in the presence of 5 M/ml of MgCI,. The resulting supernatant, which had Sm antigen activity but no RNP activity, was further concentrated by 30% saturated ammonium sulfate, lyophilized, and stored at -10°C. This partially purified Sm antigen was then used in hemagglutination to determine the Sm antibody titer.All sera were analyzed for the presence of Sm and n-RNP by passive hemagglutination (2), immunodiffusion (6), and counterimmunoelectrophoresis (7) according to pre-