A solid phase enzyme immunoassay using methylated bovine serum albumin (BSA)-precoated and DNA-coated microtiter plates was developed for the detection of IgG and IgM anti-DNA autoantibodies in the supernatants of lymphocyte cultures and hybridomas. In patients with systemic lupus erythematosus (SLE) the significantly raised IgG anti-DNA antibody synthesis indicates that preactivated anti-DNA clones circulate in the peripheral blood. This was associated with the detection of anti-DNA antibodies in the sera. The screening of 53 supernatants from human x mouse hybridomas showed an antibody to denatured DNA in 16 supernatants.