Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.