This study examined the mechanism underlying the increase of peripheral memory phenotype T cells that occurs during chronic alcohol consumption in mice. Female C57BL/6 mice were given 20% (w/v) alcohol in the drinking water for 2 weeks to 6 months. Chronic alcohol consumption significantly induced peripheral T cell lymphopenia; up-regulated expression of CD44 on T cells and increased the percentage of CD4+CD44int/hi and CD8+CD44int/hi Ly6C+ T cells; up-regulated the expression of CD43 on CD8+ T cells; increased the percentage of interferon--producing T cells; decreased the percentage of CD8+CD28+ T cells; and down-regulated the expression of CD28 on CD4+ T cells. Expression of CD25 and CD69 on peripheral CD8+ T cells was not affected and inconsistently expressed on CD4+ T cells. Neither cell type showed altered expression of CD137 or CD153. Alcohol withdrawal did not abrogate the increase in CD8+Ly6C+cells induced by alcohol consumption. In vivo bromodeoxyuridine incorporation experiments demonstrated that chronic alcohol consumption decreases naïve T cells that are presumed to have emigrated from the thymus and increases proliferation of memory T cells, but accelerates peripheral T cell turnover. Together these results indicate that chronic alcohol consumption results in T cell lymphopenia, which in turn induces T cell homeostatic proliferation that increases the proportion of peripheral memory T cells relative to naïve T cells.