It is known that smokers have a higher risk of developing cardiovascular disease and lung cancer. Plasma carotenoid concentrations in smokers are generally lower than in non-smokers and this may be due to modifications in diet or a direct or indirect action of cigarette smoke on carotenoids in the plasma. Recently it was reported that reactive nitrogen species derived from cigarette smoke could diffuse across the lung alveolar cell wall into the plasma. Such species may modify circulating low density lipoprotein (LDL) and in the process reduce circulating carotenoid concentrations. In an effort to address this rational we have treated lycopene solutions, human plasma and isolated LDL with cigarette smoke and monitored all-(E)-lycopene, 5(Z)-lycopene and beta-carotene depletion. In plasma, the depletion of all-(E)-lycopene (15.0+/-11.0%, n=10) was greater than 5(Z)-lycopene (10.4+/-9.6%) or beta-carotene (12.4+/-10.5%). In LDL, both all-(E)- and 5(Z)-lycopene were more susceptible than beta-carotene (20.8+/-11.8%, 15.4+/-11.5% and 11.5+/-12.5%, n=3 respectively). The effects have been compared with Sin-1 reactions and isomerization of all-(E) lycopene is common to both treatments. The results clearly indicate that low plasma lycopene may be a direct consequence of smoke inhalation.