Not all antioxidants reduce atherosclerosis. This may be because atherosclerosis has an autoimmune, inflammatory pathogenesis. As probucol is both an antioxidant and an immunomodulatory drug, it may be the immunomodulatory effect that underlies its ability to reduce atherosclerosis. N,N-Diacetyl-L-cystine is not an antioxidant but is immunomodulatory. In the Watanabe-heritable hyperlipidaemic rabbit model of familial hypercholesterolaemia, N,N-diacetyl-L-cystine treatment does not lower lipid levels but it does reduce atherosclerosis. Immunomodulation may be a new approach to the treatment of atherosclerosis.