The interaction between human C1q or rheumatoid factor (RF) and IgG-coated latex particles was studied by means of standard aggregometer equipment. Fresh normal human serum (NHS) prevented RF from agglutinating such particles (RF-inhibiting activity) and also disagglutinated C1q-induced particle agglutinates (C1q-disagglutinating activity). Strong evidence is presented indicating that C1 was the serum factor responsible for these activities, which were lost after complement activation of serum by IgG aggregates parallel with dissociation of C1. The normal serum range for C1q disagglutinating activity is 68–100% and for RF-inhibiting activity 92–100%. Sera from the majority of patients with systemic lupus erythematosus (SLE) had reduced C1q-disagglutinating activity (78% of the patients) and reduced RF-inhibiting activity (70% of the patients) compared to sera of healthy individuals. Those patients with greatly reduced serum activities as assayed by the present techniques were in the active phase of their disorder as judged from clinical signs and reduced total haemolytic activity. The total complement in CH50 units also correlated significantly (r = 0.73, P<0.001) with the C1q-disagglutinating activity of the patient sera. These findings together with the immunodiffusion pattern against anti-C1q and anti-C1s produced by sera from patients in the active phase of their disease suggested that circulating C1 was present in an activated and sometimes highly activated form among patients with SLE during complement consumption. Based on serial determinations it could also be excluded that functionally defective C1 was inherited or permanent among SLE patients. These techniques, which were supposed to measure functional C1 directly in serum, seemed to be sensitive and reproducible methods suitable for clinical routine in screening pathological sera and it is hoped that the methods will be useful in the treatment of patients with complement consumptive processes.