Oxidation of low density lipoprotein cholesterol (LDL-c) is supposed to play a role in the generation of atherosclerotic lesions. Grape derived beverages supply a large number of nutritional antioxidants because of their high content of polyphenols. This might be one of the mechanisms behind the supposed beneficial effect of red wine. Wine also contains alcohol and its role in oxidation processes especially in vivo is unclear. In this study the effect of daily red wine consumption for 2 weeks on oxidizability status of LDL was investigated. The role of alcohol in LDL oxidation was further explored in in vitro experiments. After abstinence from alcoholic beverages, grape juices and tea for a week, seven healthy male volunteers consumed 375 ml of red wine (30 g alcohol) per day during 2 weeks. At the start and end of the drinking period blood samples were taken and the susceptibility of LDL-c to copper-induced oxidation was analyzed with the addition of distilled water (control) and dilutions of a 12% alcohol solution, white wine and red wine. Although red wine at concentrations achievable in vivo caused a significant prolongation of the lag-time of metal ion dependent LDL oxidation in vitro (85.9+/-23.0-114.1+/-30.8 min, P<0. 001), a significant shortening of lag-time was found in vivo after the 2 weeks of wine consumption (56.3+/-13.0 min, P<0.001). A shorter lag-time compared to the control was found for both alcohol and white wine in vitro. The changed oxidizability status of LDL after 2 weeks of wine consumption made it more susceptible for the in vitro antioxidant effect of red wine. At low dilutions red grape juice extended lag-time as well, which was not influenced by the addition of alcohol. Red wine has a strong inhibitory effect on copper-induced oxidation of LDL in vitro, while red grape juice has a minor effect, an effect which should be attributed to the non alcohol components in the beverages. In vivo, however, this effect can be overshadowed by the prooxidant influence of alcohol. The balance between alcohol and polyphenols of a wine may be critical for its in vivo effect on LDL oxidation.