Ethanol may be detrimental to immune cells due to the generation of free radicals during detoxification. If this is true, then alcoholic beverages that contain antioxidants, like red wine, should be protective against immune cell damage. We investigated this by giving mice either a red muscadine wine (Vitis rotundifolia), a cabernet sauvignon (Vitis vinifera), ethanol (all at 6% alcohol) or water in the water bottles as the sole fluid for 8 wk. Plasma antioxidant capacity was measured with alphaalpha-diphenyl-beta-picrylhydrazyl and was more than doubled in the mice that consumed wine compared to control mice that consumed water or ethanol. Cytochrome P450-2E1 levels and glutathione-S-transferase activity were modified in such a way as to be interpreted as protective. An immune response was elicited by an intraperitoneal injection of lipopolysaccharide. Later (24 h), natural killer cells and T-lymphocytes derived from the circulation were quantitated in the leukocyte fraction by flow cytometry. Ethanol consumption, as ethanol, significantly suppressed baseline cell numbers relative to the other groups. However, the mice that consumed the same amount of alcohol as wine had baseline cell numbers not different from the water-consuming controls. The lymphocyte response to lipopolysaccharide challenge was inhibited in the mice that consumed ethanol, but was normal in those that consumed the same amount of alcohol in the form of wine. We conclude that there are phytochemicals acting as antioxidants and impacting on the detoxification pathway in the wine that offset the detrimental effects of ethanol on immunity.