Several plasma and membrane proteins belong to a superfamily of structurally related proteins that contain internal homology of a variable number (2-30) of repeating units. Each SCR (short consensus repeat) unit is approximately 60 amino acid residues in length, with the positions of 1 Trp, 2 Pro, and 4 Cys residues being conserved. The aim of this study was to provide experimental evidence that each SCR may exist as an independent structural domain maintained by disulfide bonds. The well-characterized C4b-binding protein (C4BP) with eight SCR units in each of its seven identical chains was chosen for this study. Analysis of the disulfide-bonding pattern indicated that intrachain disulfide bonds may be localized within each SCR unit, with the first and third and the second and fourth half-cystines in each unit being linked. This pattern of disulfides may confer to C4BP (and to other structurally related proteins) a conformation which apparently allows the assembly of the SCR units (4-30) in a tandem fashion. Such an arrangement of the polypeptide chain(s) may explain, in part, the elongated shape of these protein molecules. The structural motif of the SCR units of C4BP is discussed in relation to those previously described for the type II domain of fibronectin and the kringle structure present in various proteins of the coagulation system.