EPR spectroscopy has been employed to study the rates and mechanisms of reactions of copper/peroxide/thiol systems relevant to biological conditions, with especial emphasis on the oxidation by Cu^II of the antioxidant glutathione (GSH) to GSSG (and Cu^I) and the subsequent generation of hydroxyl radicals from reaction between Cu^I and H₂O₂. Evidence is presented that the reaction between Cu^II and GSH in water proceeds considerably more rapidly than with cysteine or penicillamine (for which relatively stabilized S₂N₂-coordinated copper complexes are involved) but that the reoxidation of the copper proceeds relatively slowly for glutathione via the reaction of the complex Cu^ISG with H₂O₂.