The beta chain of human fibrinogen is composed of 452 +/- 5 amino acid residues, 14 of which are methionines. Consistent with these findings we have isolated and characterized 15 fragments after cyanogen bromide digestion of carboxymethylated beta chains. The arrangement of several of these peptides was deduced on the basis of overlapping peptides isolated from the fragments D and E produced by the plasmic digestion of fibrinogen and/or from a tryptic digest of citraconylated beta chains. Most of the other cyanogen bromide fragments can be aligned by homology with the alpha and/or gamma chains from human fibrinogen, although the positioning of a few of the smallest peptides is still ambiguous. The homology of the beta chain with the gamma chain is especially strong in certain regions of the domain that includes fragment D.