Objectives-Antibodies against Clq (ClqAb) have been demonstrated in the serum of patients with several immune complex diseases. Patients, particularly those with lupus nephritis, were found to have increased serum titres of IgG ClqAb in a cross-sectional analysis. In the present prospective study correlations were sought between serum titres of IgG ClqAb and clinical as well as laboratory parameters of disease activity in patients with systemic lupus erythematosus (SLE). Methods-Titres of IgG ClqAb in the serum of 68 SLE patients were measured serially during a three year period. At the same time clinical and laboratory parameters of disease activity were assessed. Results-Increased titres of IgG ClqAb were found in the serum of 56% of SLE patients during the study. Significant correlations were found between increased titres of IgG ClqAb and renal involvement. Clinical signs of renal involvement were found to be associated with significant increases of serum titres of IgG ClqAb in the six months preceding this appearance: Fifty per cent of the increases in serum titres of IgG ClqAb were followed by the development of renal involvement. Elevated serum titres of IgG ClqAb were especially related to proliferative forms of glomerulonephritis. Furthermore, significant correlations were found between serum titres of IgG ClqAb and serum levels of immune complexes, levels of complement components, and titres of antibodies to DNA. Conclusions-The results suggest that IgG ClqAb play a pathogenic role in the development of lupus nephritis and that serial measurement of serum titres of IgG ClqAb is useful in the management of SLE patients.