This study examines the effect of cysteine on the auto-oxidation of homocysteine, a process that has been implicated in the pathologic mechanism of hyperhomocystinemia with respect to arteriosclerosis and vascular disease. It is shown that homocysteine autoxidizes at a much slower rate than cysteine, but that low concentrations of cysteine or cystine dramatically accelerate homocysteine oxidation and increase the rate of homocysteine-dependent oxygen consumption. It is proposed that the major role of homocysteine is to reduce cystine to cysteine, and that cysteine autoxidation is the mechanism by which thiol-dependent oxidative stress occurs.