The majority of C1q-binding IgG in sera of some patients with systemic lupus erythematosus (SLE) cosediments with monomeric IgG. This study was undertaken to provide definitive proof that the low-molecular weight C1q-binding IgG consists of autoantibodies to C1q. Monomeric C1q-binding IgG was isolated from five SLE plasmas by C1q affinity chromatography and gel filtration. All C1q-binding IgG preparations and their F(ab')2 fragments bound to both C1q and the collagen-like region of C1q by an ELISA. To rule out the possibility that small DNA-antiDNA immune complexes caused this binding activity, Fab' fragments of the C1q-binding IgG preparations were digested with DNase I to degrade any DNA. The Fab' fragments continued to bind to C1q and its collagen-like region after this treatment. C1q-binding IgG was heterogenous on isoelectric focusing. Interaction of C1q-binding IgG with solid-phase C1q was retained in 1 M NaCl, whereas the binding of DNA or heat-aggregated IgG to solid-phase C1q was abrogated or markedly diminished. The association constant of C1q-binding IgG with solid-phase C1q was 2.7 X 10(7) M-1. We conclude that low-molecular weight C1q-binding IgG in the studied patients with SLE consists of autoantibodies to the collagen-like region of C1q.