Thiobarbituric acid reactive substances (TBARS) in 38 low density lipoprotein (LDL) samples from 21 healthy male non-smokers and 17 smokers (greater than 20 cigarettes per day) were measured before and after oxidation. TBARS in the freshly isolated LDL from non-smokers and smokers were similar, however, oxidized LDL samples from smokers developed nearly twofold more TBARS than non-smoker LDL samples. 16 LDLs from 8 smokers and 8 non-smokers were conditioned in redox-metal containing F-10 medium and subsequently added to P 388 D.1 macrophage cultures. LDL dependent cholesteryl ester increase in the P 388 D.1 cells after an 18 h incubation with non-smoker LDL was significantly lower than in the cells incubated with smoker LDL (P less than 0.01). A higher reacylation rate of cholesterol in P 388 D.1 cells incubated with smoker LDL (P less than 0.05) suggests that LDL-cholesterol uptake is significantly higher in P 388 D.1 cells incubated with smoker-LDL than in P 388 D.1 cultures exposed to non-smoker LDL. This finding indicates that smoking might contribute to increased shunting of LDL into macrophages. The vitamin E content of 6 non-smoker LDL samples was significantly higher than that in 6 smoker-LDL samples (P less than 0.01). We conclude that the vitamin E/LDL ratio may differ significantly in heavy smokers and non-smokers.