It has been suggested that the generation of cysteine (Cys-SH) by cells may play a role in the initiation of oxidation of low density lipoprotein (LDL). Cysteine has long been considered as an antioxidant. We studied the effect of Cys-SH on the oxidation of LDL by copper. The presence of Cys-SH had a profound inhibitory effect on the formation of conjugated dienes when fresh LDL was used. However, when we used LDL samples that were subjected to pre-incubation with copper, a progressive decrease in the inhibition and an actual enhancement of oxidation by Cys-SH could be demonstrated. The oxidation of freshly prepared LDL by RAW macrophages as compared to older LDL was considerably less. The addition of Cys-SH inhibited the oxidation of LDL by cells. In contrast, the addition of cystine (Cys-S-S) enhanced the oxidation of older LDL preparations while such additions had no effect on the oxidation of freshly prepared LDL. When pre-incubated LDL was subjected to oxidation by cells an enhancement of oxidation by Cys-S-S could be noted. These results demonstrate that the role of Cys-SH generated as a result of cellular recycling of Cys-S-S in the oxidation of LDL may not relate to the initiation of oxidation reactions. However, Cys-SH may enhance the rate of oxidation of LDL that may contain peroxides.