The presence of elevated plasma levels of autoantibodies against C1q, a subcomponent of the first component of complement in sera of patients with systemic lupus erythematosus (SLE) has been found to be associated with renal involvement. The purpose of this study was to determine whether increases in anti-C1q antibodies (anti-C1q) precede renal involvement in SLE. Forty-three SLE patients were studied longitudinally to determine the relationship between manifestations of the disease and levels of anti-C1q as well as to identify antibodies against double-stranded DNA (anti-dsDNA). Increased levels of anti-C1q were detected in all 14 of the patients who developed proliferative lupus nephritis out of 17 patients with renal relapses, which was significantly more frequent (P < 0.005) than in patients with nonrenal relapses (six of 16 patients) or with inactive disease (two of 10 patients). Increased anti-dsDNA levels were observed in 14 of 17 patients with renal relapses compared with 15 of 16 patients with nonrenal relapses and five of 10 patients with inactive disease. Significant increases in anti-C1q levels prior to the relapse occurred in 10 of 14 patients who developed proliferative nephritis and in three of 16 patients with nonrenal relapses. Significant increases in anti-dsDNA levels occurred in 11 patients of the former group and in nine patients of the latter group. No significant increases in anti-C1q or anti-dsDNA levels were observed in the patients with inactive disease. The mean time period between the occurrence of a significant increase in anti-C1q or anti-dsDNA level and the moment of renal relapse for both antibodies was 2.3 months. These results suggest that an increase in anti-C1q level has a predictive value for an ensuing renal relapse of proliferative lupus nephritis, and that serial measurements of anti-C1q levels might be useful in the management of SLE patients.