An evaluation of the diagnostic value of low avidity antibodies to double stranded DNA (dsDNA) measured by the polyethylene glycol (PEG) assay was undertaken. By routine screening low avidity anti-dsDNA were detected in the serum samples of 106 hitherto unknown patients. Clinical data of these patients were collected and when only low avidity anti-dsDNA was present (n = 92) a varied disease spectrum was observed. A diagnosis of systemic lupus erythematosus (SLE) was established in 48/92 (52%), lupus-like disease in 21/92 (23%), autoimmune hepatitis in 9/92 (10%), rheumatoid arthritis in 8/92 (9%), and mixed connective tissue disease in 2/92 (2%) of all patients. Patients with definite SLE were all older than 45 years and predominantly female (46/48, 96%). They showed a remarkably low incidence of renal disease (2/69, 3%). When high avidity antibodies to dsDNA as measured by the Farr assay were present as well (n = 14) a diagnosis of SLE could be established in 12/14 (86%) of all patients, indicating the secondary importance of low avidity anti-dsDNA in these patients.