Sera obtained from 53 patients with systemic lupus erythematosus (SLE) were investigated for the presence of immunoglobulin class-specific antibodies against native (ds)DNA and denatured (ss)DNA. The methods employed were the Crithidia luciliae test and an enzyme-linked immunosorbent assay (ELISA), respectively. Anti-dsDNA antibodies of IgG class were seen in 42%, IgM-anti-dsDNA antibodies in 43%, and IgA-anti-dsDNA antibodies in 30% of the patients. There was an association between the presence of both IgG- and IgA anti-dsDNA antibodies and the activity of the disease. Patients with active nephritis also had anti-dsDNA antibodies of IgG and IgA class significantly more often than patients with inactive nephritis or without renal disease. IgG-anti-ssDNA antibodies were seen in 89%, IgM-anti-ssDNA antibodies in 51%, and IgA-anti-ssDNA antibodies in 66% of the patients. Patients with nephritis had low levels of antibodies to ssDNA of IgM class. We suggest that immunoglobulin class-specific anti-DNA antibodies should be determined in the diagnosis and monitoring of SLE.