The present study investigated the redox-consequences of the interaction between various endogenous thiols (RSH)-glutathione, cysteine, homocysteine, γ-glutamyl-cysteine, and cysteinyl-glycine- and Cu2+ ions, in terms of their free radical-scavenging, ascorbate-oxidizing and O2{radical dot} --generating properties of the resulting mixtures. Upon a brief incubation (3-30 min) with Cu2+, the free radical-scavenging properties (towards ABTS{radical dot}+ and DPPH{radical dot}) and thiol-titrateable groups of the RSH added to the mixtures decreased significantly. Remarkably, both effects were only partial, even in the presence of a large molar Cu2+-excess, and were unaffected despite increasing the incubation time. At equimolar concentrations, the RSH/Cu2+ mixtures led to the formation of (EPR paramagnetic) Cu(II)-complexes that were time-stable and ascorbate-reducible, but redox-inactive towards oxygen. In turn, at a slight molar thiol-excess (3:1), the mixtures resulted in the formation of time-stable Cu(I)-complexes (EPR silent) that were unreactive towards ascorbate and oxygen. The only exception was seen for the thiol, glutathione, whose mixture with Cu2+ mixture displayed a O2{radical dot} --generating capacity (cytochrome c- and lucigenin-reduction). The data indicate that, depending on their molar ratio, the interaction between Cu2+ and the tested thiols would give place to mixtures containing either: (i) time-stable and ascorbate-reducible Cu(II)-complexes which display free radical-scavenging properties, or (ii) time-stable but redox-inactive towards oxygen Cu(I)-complexes. Among the latter, the only exception was that of glutathione. © 2008.