The 8.12 idiotype defines a population of anti-DNA antibodies present in the serum of patients with systemic lupus erythematosus. As part of our studies to elucidate the genetic origin and structural features of anti-DNA antibodies, we examined monoclonal immunoglobulin (Ig)-containing sera from 706 patients for expression of the 8.12 idiotype. We found 41 such sera to have significant 8.12 reactivity (greater than 4 SD above the mean of normal controls) and demonstrated that in 24 of these sera (8 IgM, 14 IgG, and 2 IgA) this reactivity could be localized to the monoclonal protein. In addition, 12 of the 8.12-reactive monoclonal Ig (11 IgG and 1 IgA) bind dsDNA. In the other 17 sera, the 8.12 reactivity could be attributed to polyclonal antibody. These findings provide further evidence that the serum monoclonal Ig frequently express the antigenic and idiotypic reactivities of autoantibodies. Furthermore, these data support the contention that anti-DNA specificity may result from somatic diversification of germ-line Ig gene sequences.