S era of 27 members of 3 human kindreds with familial systemic lupus erythematosus (SLE) were examined for expression of a cross-reactive idiotype present on anti-DNA antibodies of SLE patients. By radioimmunoassay, serum samples from 6 of 8 SLE patients and 15 of 19 family members had high-titered reactivity with the antiidiotype, 3I. Isoelectric focusing and Western blot analysis of 3I-reactive bands revealed two patterns of reactivity: either a pattern of bands present at pH 5-7, or bands present at pH 5-7 with additional bands present at pH 7-8.5. Cationic bands were found to correlate with the presence of anti-DNA antibodies, indicating that immunoglobulin charge may be a factor in determining specificity for DNA. Millipore filter analysis revealed anti-DNA antibodies in sera of 4 of 8 SLE patients and 2 of 19 family members without SLE. In 2 additional SLE patients and 2 additional family members, anti-DNA antibodies were revealed when sera were analyzed under conditions that dissociate immune complexes. This study indicates that expression of an idiotype associated with anti-DNA antibodies is significantly increased in relatives of SLE patients and usually occurs in the absence of anti-DNA activity.