In order to evaluate the practical clinical value of centromere, Scl-70, and nucleolar antibodies as demonstrated routinely by the Autoimmune Department of the Serum Institute of Copenhagen, 1293 sera from 497 patients with scleroderma (SSc) and other connective tissue diseases were tested for the three antibodies and for other nuclear antibodies. The three antibodies were found in 32, 15 and 15%, respectively, of sera from patients with SSc. Since more than one of the three antibodies was rarely demonstrated in any one serum, one of them was found in two thirds of sera from patients with SSc. The specificity of the three antibodies for SSc was 95% or more. Centromere antibody was found most frequently in patients with limited SSc. Scl-70 antibody was found almost exclusively in sera from patients with extensive SSc (involving the skin of the trunk). In such sera, centromere antibody was found in only 21%. Scl-70 antibody was overrepresented and centromere antibody was underrepresented in sera from patients with pulmonary involvement, the converse being true for sera from patients with calcinosis, esophageal involvement and telangiectasia.