The sensitivities and the specificities of Crithidia luciliae immunofluorescence, (CL-IF), counterimmunoelectrophoresis (CIE), and enzyme-linked immunosorbent assay (ELISA) as aids to the clinical diagnosis of systemic lupus erythematosus (SLE) were compared to determine which was the single most useful test in the management of this disease. The patients who had SLE were further divided into those with active or inactive disease and those with and without nephritis in an attempt to determine whether any of these tests could reliably differentiate these groups. Results obtained by these tests, together with those of a nonspecific antinuclear antibody assay used as a screening test, were compared with results for other autoimmune diseases. Although the ELISA was more often positive than CIE and CL-IF in cases of SLE, CL-IF had the highest specificity for SLE, giving no positives in any of the other autoimmune diseases examined. None of the tests satisfactorily differentiated active from inactive SLE or consistently detected the presence or absence of nephritis in SLE.