In humans, homozygous deficiency of the first component of the classical pathway of complement, C1q, is a powerful disease susceptibility factor for the development of systemic lupus erythematosus (SLE). This strong association indicates that a functional activity of C1q protects from the development of SLE. Studies in vitro have shown that C1q can bind apoptotic keratinocytes suggesting that it may have an important role in the clearance of apoptotic cells. C1q-deficient mice, generated by gene targeting, showed an increased mortality and 25% of the mice had histological evidence of glomerulonephritis characterised by multiple apoptotic cell bodies and immune deposits, assessed by immunofluorescence and electron microscopy. These observations are compatible with the hypothesis that C1q deficiency causes autoimmunity by an impaired clearance of apoptotic cells.