Remarks: The detection of circulating antibodies to nuclear antigens is an important tool in the investigation of systemic rheumatic diseases. The dsDNA antibodies are found mainly in SLE (Systemic Lupus Erythematosus) and are important for diagnosis of that condition as well as for monitoring the treatment. IgG antibodies to ds-DNA are present in 60% of active SLE cases. They may be present in smaller fractions of patients with other rheumatic disorders and in chronic active hepatitis, infectious mononucleosis, and biliary cirrhosis. In part, sensitivity for the different diseases is methodology dependent, and correlation with local laboratory experience is necessary. In the past it was a rule of thumb that it was unnecessary to test for anti-DNA in patients with a negative test for Antinuclear antibodies (ANA Hep-2 cells). A group of "ANA-negative" lupus patients has been described with Anti-ss-DNA and Anti-SS-A/Ro and Anti-SS-B/La. However, HEp-2 substrate is much more sensitive than frozen section substrates; and it is uncommon for Anti-SS-A/Ro to be negative with such substrates. Procainamide and hydralazine may induce Anti-ss-DNA antibodies and Anti Histone antibodies. Following liters of anti-DNA antibody may be of use in evaluating response to therapy, but should be regarded as a guide rather than a rigid dictator of treatment. Titers correlate with activity of lupus nephritis, but ANA and anti-DNA antibodies are less reliably related to active progressive lupus glomerulonephritis than are Complement C3 and CH50 complement depression. Antibodies to ss-DNA are not as diagnostically useful as those against ds-DNA which are associated with renal disease and clinical activity. Patients at risk for severe nephritis are characterized by persistent abnormal urinalysis, high levels of anti-ds-DNA and/or diminished complement. Other tests relevant to SLE additional to the complements include CBC, ESR, urinalysis with urine sediment microscopy, urinary protein excretion, and creatinine. Creatinine and creatinine clearance, however, are relatively insensitive to deterioration of glomerular filtration rate in lupus nephritis.