The aim of this study was to compare ongoing production of anti-C1q antibodies (anti-C1q) in peripheral blood with serum anti-C1q levels in patients with systemic lupus erythematosus (SLE), especially in patients with nephritis. Using the ELISPOT technique for the detection of IgG and IgA anti-C1q production, 21 patients with active SLE were investigated. ELISAs for IgG and IgA anti-C1q were compared with the ELISPOT results. Six of the patients were found to have proliferative nephritis (WHO grade III/IV) confirmed by renal biopsy. High numbers of IgG anti-C1q spot-forming cells (SFC), defined as > 20/10(5) plated peripheral blood mononuclear cells (PBMC), were exclusively observed in patients with proliferative nephritis (P < 0.0001). Serum levels of IgG anti-C1q were significantly increased in patients with proliferative nephritis (P = 0.039). High ongoing IgG anti-C1q production was observed in all patients with proliferative nephritis, which may be a contributory factor in the pathogenesis of this disorder. The detection of IgG anti-C1q production may be valuable in the clinical investigation of patients with suspected SLE nephritis.