Bronsted coefficients were determined for the rates of thiol-disulfide interchange between low MW thiols and the disulfide groups of 4 native or modified proteins: DNase (.beta.nuc .simeq. 0.36), lysozyme (.beta.nuc .simeq. 0.55), adenylate kinase(SSCH3)2 (.beta.nuc .simeq. 0.65) and papain(SSCH3) (.beta.nuc .simeq. 0.45). These values are similar to those observed for reductions of oxidized glutathione and Ellman''s reagent [5,5''-dithiobis(2-nitrobenzoic acid)] by a similar set of thiols (.beta.nuc .simeq. 0.5). Glutathione is anomalously slow in reduction of certain protein disulfide groups; although this effect may in part reflect steric hinderance to attack by the relatively large glutathione molecule at disulfides shielded by protein tertiary structure, other (presently undefined) factors also appear to be important, at least in the case of DNase. The rates of reduction of several disulfide derivatives of papain(SSR) by dithiothreitol were determined. These data provide estimates of the Bronsted coefficient for the central thiol in thiol-disulfide interchange: these estimates fall in the range .beta.c .simeq. -0.25 to -0.43. Rates of reduction of protein disulfide moieties were analyzed by using a Bronsted equation developed previously to yield pKa values for the participating thiol moieties: in particular, for papain, pKa (Cys-25) = 8.4 at pH 9 and pKa (Cys-25) = 4.1 at pH 6. The thiols of the structurally essential cysteine group of lysozyme seem to have pKa .simeq. 11. The advantages and disadvantages of this method for estimating thiol pKa values are discussed.