The objective of this study was to determine if chronic ethanol consumption could modify cell populations in the Peyer's patches (PP), which could favor pathogenic or opportunistic infections in mice, as seen in chronic alcohol addicts. Young C57BL/6 mice receiving the Lieber-DeCarli diet (36% of calories as ethanol) for 5 weeks presented a significant decrease in the total number of cells in the PP. Mature FVB mice receiving the Lieber-DeCarli diet for 19 weeks presented a highly significant decrease in the total number of cells and in the absolute number of T and B cells in the PP. Young C57BL/6 mice receiving the 100% NRC (30% ethanol) or the 60% NRC (30% ethanol) diets for 7 weeks presented alterations in the T and B cell phenotype comparable with the alterations observed in mice receiving the Lieber-DeCarli diet for 19 weeks. As less alcohol for a shorter time caused similar changes to those seen with a highly micronutrient enriched diet with more alcohol for a longer consumption period, micronutrient supplementation may overcome some immune damage found in animal models of alcoholism. Our data indicated that ethanol administration altered the mucosal immune system at the level of the PP, the site for antigen presentation and induction of a mucosal immune response.