Serial serum samples from 48 patients with systemic lupus erythematosus (SLE) were assayed for C3, anti-DNA antibody, and circulating immune complexes (CIC). CIC were measured by the fluid phase (FClq) and solid phase (SClq) Clq binding assays. Elevations of the SClq results were associated with the presence of manifestations of SLE (P less than 0.001), including active renal disease (P less than 0.005) and arthritis (P less than 0.001), as well as changes in degree of disease activity which prompted physician action. A change in the SClq results correctly predicted a change in disease activity 82% of the time (P less than 0.005). Abnormalities of FClq, anti-DNA antibody, and C3 were neither associated with nor predictive of changes in disease activity of SLE. These data suggest that the SClq method of determining CIC is the most reliable laboratory indicator of clinical activity in SLE.