The detection of antibodies to DNA is one of the most important laboratory tests in rheumatology and immunology from both scientific and clinical points of view. The most useful methods for detection of anti-DNA are the liquid phase radioimmunoassay (Farr assay), solid phase enzyme-linked assays (ELISA) and immunofluorescence (Crithidia Luciliae). The clinical value of detection of anti-DNA can be summarized as follows: (a) Antibodies to DNA (particularly those reactive primarily with double-stranded DNA determinants) are highly specific for the disease SLE; (b) Levels of anti-DNA bear a close relation to disease activity in many patients. Rapidly rising levels are frequently associated with a subsequent exacerbation and clinical improvement is often accompanied by declining levels of anti-DNA. However, a minority of patients may have persistent elevations of anti-DNA for extended periods in the absence of overt clinical disease activity; (c) Although a single determination of anti-DNA has little prognostic value, the persistent presence of high levels or the absence of anti-DNA may define patient subsets with poor and good prognoses respectively; (d) Antibodies to single stranded DNA although present in some patients with discoid lupus and "ANA-negative" lupus, have little diagnostic specificity and are less valuable for disease follow-up as compared with antibodies to double-stranded DNA.