The equilibrium cleavage reactions of keratin disulfide with sulfite and mercaptans were studied. Experimental cleavage levels approximate closely those calculated on the basis of a derived equilibrium expression for the reaction employing the ionization constants of the reactants and reaction products. A generalization of the equilibrium analysis leads to the conclusion that in any nucleophilic attack on the disulfide bongs, the effect of pH on the equilibrium will depend primarily on the relative pK values of the thiol group of keratin and the attacking nucleophile. The pK of keratin thioil groups was determined by a novel swelling technique.