Although anti-DNA antibodies are generally considered to be specific markers for systemic lupus erythematosus (SLE), antibodies binding DNA from certain bacterial species can be found in the sera of normal subjects. To characterize the immunochemical properties of these antibodies, the IgG subclass and light chain profile of antibodies to single-stranded micrococcal DNA (MC DNA) in the sera of normal subjects and patients with SLE was determined. The anti-MC DNA response in normal sera was predominantly of the IgG2 subclass with a marked predominance of kappa light chains. In contrast, anti-MC DNA antibodies in SLE sera exhibited all IgG subclasses with a predominance of the IgG1 subclass and both kappa and lambda light chains were represented. These results suggest that antibodies to bacterial DNA in the sera of normal subjects and patients with SLE differ in patterns of immunoglobulin gene expression; the restricted response of normal subjects may be related to the binding to a discrete DNA determinant.