Indirect evidence for the complement-fixing site of human IgG1 has been found by using chemical modification of the immunoglobulin. These results implicate the amino acid residues, tryptophan, tyrosine, and arginine. Furthermore, by the use of synthetic peptides it has been shown that the area surrounding the tryptophan and tyrosine at positions 277 and 278 probably constitutes the locus of the complement-fixing site of human IgG1. By analogy, the tryptophan at position 488 of human IgM is implicated in the complement-fixing site of this immunoglobulin. Evidence for this is presented by a peptide which mimics the sequence 487-491 of human IgM and possesses the ability to consume complement. The relative complement-fixing ability of this peptide is 200 times less effective than human IgG1.