It is well established that development of conformational structure depends on amino acid sequence, although the exact relationship (which would make posible a precise prediction of native conformation from a knowledge of primary structure) remains unclear. It is widely accepted that native conformation develops from the randomly coiled chain of the denatured (or newly synthesized) protein by a process of nucleation, whereby a progressive folding, governed by thermodynamic factors, prevails until the native conformation is reached. As a consequence, the formation of S-Sbonds would have nothing to do with folding but would occur in the latter stages to stabilize the native structure. However, it has been observed in this laboratory that native secondary structure is dependent on the existence of S-S bonds to the extent that the half reduced form assumes a circular dichroic behavior indistinguishable from that of the fully reduced protein. Further work is in progress to clarify the role of S-S bonds in chain folding.