The oxidative folding of proteins is reviewed and illustrated with bovine p
ancreatic ribonuclease A (RNase A). The mutual effects of conformational fo
lding and disulfide bond regeneration are emphasized, particularly the "loc
king in" of native disulfide bonds by stable tertiary structure in disulfid
e intermediates. Two types of structured metastable disulfide species are d
iscerned, depending on the relative protection of their disulfide bonds and
thiol groups. Four generic pathways for oxidative folding are identified a
nd characterized.