The possible influence of smoking on the low-density lipoprotein (LDL) and its biological activity was investigated. Plasma LDL was prepared from healthy male smokers and nonsmokers, and oxidized with Cu (II) as prooxidant. Oxidized LDL from smokers generated significantly more lipid peroxidation products, so-called thiobarbituric acid reactive substances (TBARS), when compared to oxidized nonsmoker LDL. Analysis of vitamin E levels in LDL obtained from both smokers and nonsmokers revealed that the vitamin E content of smoker LDL was significantly less than that of nonsmoker LDL. The amounts of cholesteryl esters formed in cultured P388. D.1 macrophages were greater in the presence of smoker LDL than with nonsmoker LDL. The data suggest that some of the proatherogenic effects of smoking may be related to oxidative modification of LDL and alteration of its biological activity.