The simultaneous appearance of autoantibodies with either a functional or structural relationship to anti-C1q antibodies (anti-C1q) was investigated in 39 systemic lupus erythematosus (SLE) patients and in 28 rheumatoid arthritis (RA) patients, in both cross-sectional and longitudinal design. Levels of anti-C1q showed an isotype-specific correlation to levels of immune con-glutinin (IK) in SLE patients, whereas no correlation was evident to levels of antibodies to the structurally related antigen type II collagen (anti-CII) in SLE or RA patients. IgG anti-C1q levels correlated with serum levels of the terminal complement complex (sC5b-9) in SLE patients. In two longi-tudinally followed patients, the IK response preceded the anti-C1q response. Possibilities for regulation of the humoral anti-complement response are discussed.