Antibody to native DNA was measured by five techniques: the Crithidia luciliae immunofluorescence (CL-IF) test; filter radioimmunoassays using either untreated human KB DNA, endonuclease-treated KB DNA, or a synthetic polynucleotide (poly dAT); and the Farr immunoprecipitation assay using KB DNA. The specificity and sensitivity of the CL-IF assay was similar to that of the filter radioimmunoassay procedures using KB DNA. The CL-IF test showed an increased frequency of positive tests in patients with active disease and severe renal involvement. In patients with severe renal involvement, high titers of serum nDNA antibodies were measured by this procedure. A unique advantage of the CL-IF test was its ability to identify complement-fixing nDNA antibody. The presence of such antibody was correlated with high antibody titer and the presence of severe renal disease. The CL-IF assay is a simple and useful procedure for measurement of anti-nDNA.