To examine the effects of smoking on lymphocyte subpopulations, we measured the following cell subpopulations: CD4+ T-cell subpopulations (i.e., CD4+CD29+, CD4+CD45RO+, and CD4+CD45RA+ cells); CD8+ T-cell subpopulations (i.e., CD8+CD11a+ and CD8+CD11b+ cells); and natural killer cell subpopulations (i.e., CD16+CD57-, CD16+CD57+, and CD16-CD57+ cells). We measured these subpopulations, together with total CD4+ T, total CD8+ T, total CD3+ T, B (CD19+), and total lymphocytes, in 10 male heavy smokers, 38 male light-to-moderate smokers, and 33 male nonsmokers. The mean ages were 30 y, 31 y, and 32 y, respectively, and ages did not vary significantly among the smokers. CD4+CD29+ and CD4+CD45RO+ (memory T) cells in heavy smokers were significantly more numerous than those in light-to-moderate smokers and nonsmokers. Also, these memory T-cell subpopulations were significantly more numerous in light-to-moderate smokers than in non-smokers. The number of CD4+CD45RA+ (naive T) cells was significantly larger in heavy smokers than nonsmokers; numbers of CD4+CD45RO+ T and CD4+CD29+ T cells (memory T cells) were significantly correlated with daily cigarette consumption. Numbers of CD3+ T, CD4+ T, CD19+ B, and total lymphocytes in heavy smokers were significantly larger than in nonsmokers. There were significantly more CD3+ T, CD4+ T, and total lymphocytes in light-to-moderate smokers than in nonsmokers. The numbers of CD4+ T lymphocytes in heavy smokers were significantly larger than in light-to-moderate smokers. Perhaps CD4+ T cell subpopulations, especially memory T cells, are most susceptible to the effects of smoking on lymphocyte subpopulations.