The peroxide-coupling kinetics and various pK, values of cysteine and glutathione have been determined over a range of conditions. In the pH range 6-12 and the temperature range &35"C, both sulfhydryl compounds react with hydrogen peroxide (in the neutral, undissociated form) according to the same SN2 mechanism that applies to thiol compounds, i.e. RS-+ H,02 a RSOH +OH-(rate-limiting) RS-+RSOH-RSSR+OH-. The reaction involves neither a metal catalyst nor free-radical intermediates; it yields disulfide product essentially quantitatively. The rate law is given by d[RSH] ------=2k[RS-] [H,O,]=k.[RS-] [H202]exp[--E./RT] dt where k, and E, are 1.77 x 10"' (M s)-' and 51.0 kJ/mol, respectively, for cysteine, and 2.10 x lo9 (M s)-' and 46.9 kJ/mol, respectively, for glutathione. The pK, values of the sulfhydryl compounds vary with temperature according to PK.=&&='(;)--s]. Parameter values of AH and AS are reported for the various proton groups. The nonradical nature of the peroxide-coupling reactions suggests that, in biological systems, the immunological function of sulfhydryl compounds against radical toxicity may derive less from a direct scavenging of radicals than from the removal of hydrogen peroxide as a source of their formation. Moreover, the rapidity and spontaneity of the S,2 reactions suggests that the function of sulfhydryl peroxidase may he less rate enhancement than the control of the reactive and otherwise harmful sulfenic acid intermediates.