We examined the effect of DNase treatment of sera with antihistone activity. In non-systemic lupus erythematosus (SLE) sera, antihistone levels remained unmodified, but a significant decrease was observed in 7 of 11 SLE sera with anti-DNA antibodies. This was accompanied in some by an increase in anti-DNA levels. We therefore considered that DNA-anti-DNA complexes were being detected, as part of the antihistone activity in SLE patients, by binding of the complexes through their DNA to the histones used in the assay. This was confirmed by demonstrating that DNA-anti-DNA complexes formed in vitro, and by studies performed with monoclonal antibodies with affinity to double-stranded DNA and/or histones.