The complement fixing ability of the F(ab') 2 fragment of human IgG was studied using an immune precipitate (Ippt) formed between tetanus toxoid and the F(ab') 2 of high-titer IgG antibody against tetanus toxin. A major subclass of the specific IgG antibody against tetanus toxin, which was separated by affinity column chromatography, was identified as IgG 1. On incubation of normal human serum (NHS) with the Ippt formed at equivalence, a dose-dependent consumption of CH50, C3 and C5 activities was observed without significant loss of the early acting complement components. A similar consumption of CH50, C3 and C5 activities was found in NHS reacted with Ippt formed at any antigen/antibody ratio. The Ippt formed at antibody excess was more efficient in complement consumption than the Ippt formed at antigen excess. An apparent consumption of C3 and C5 activities was also noted in C4-deficient guinea pig serum treated with Ippt. When Ippt was incubated with Mg 2+-EGTA-treated NHS, both C3 and C5 convertases of the alternative pathway were generated on the Ippt. From these results, it was concluded that the F(ab') 2 of human IgG antibody, especially IgG 1 antibody, when it formed an Ippt with antigen, could activate the alternative complement pathway.