A commercially available enzyme immunoassay system for detecting autoantibodies to double-stranded DNA, deoxyribonucleoprotein, Smith, ribonuclearprotein, Sjögren's syndrome-associated antigens A and B, and scleroderma-associated antigen 70 was compared to the conventional immunofluorescence assay for double-stranded DNA and double diffusion assays for extractable nuclear antigens. There was excellent correlation between methods, but it appears that the enzyme immunoassays are more sensitive. Based on the results of this study, the authors recommend performing anti-nuclear antibody screening at two dilutions, with enzyme immunoassay follow-up of appropriate patient sera that are positive on anti-nuclear antibody testing. Nucleolar and centromere pattern anti-nuclear antibodies are diagnostic for variants of scleroderma and need no further evaluation. Negative anti-nuclear antibody tests performed using HEp-2 tissue culture cells require no further evaluation.