To investigate the influence of cigarette smoking on mononuclear cell subsets, we determined T cell, B cell, monocyte, and HLA-DR+ subsets in a population-based, stratified, random sample of healthy Caucasians using monoclonal antibodies and flow cytometry. The study population consisted of 282 subjects 20 to 69 yr of age, including 108 smokers and 174 nonsmokers. Multivariate analysis techniques were used to assess the influence of cigarette smoking status after controlling for the effects of age and gender. Cigarette smoking was associated with a nonspecific increase in the leukocyte count involving all major cell types (smokers: 8.50 +/- 0.15 versus nonsmokers: 7.33 +/- 0.12 cells/mm3; p less than or equal to 0.0001). In addition, cigarette smokers had a selective increase in CD4+ cells (helper-inducer T cells) compared with nonsmokers (55.3 +/- 0.8 versus 52.2 +/- 0.6% of lymphoid cells; p = 0.002), resulting in a statistically significant increase in the CD4+/CD8+ (helper/suppressor) ratio (2.42 +/- 0.1 versus 2.13 +/- 0.16; p = 0.02). There was no significant difference between smokers and nonsmokers in the level of CD3+ cells (total T cells: 76.8 +/- 0.7 versus 76.1 +/- 0.5; p = 0.5), CD8+ cells (suppressor-cytotoxic T cells: 25.7 +/- 0.8 versus 27.0 +/- 0.5%; p = 0.1), CD19+ cells (B cells) (10.7 +/- 0.4 versus 10.0 +/- 0.3%; p = 0.2), CD14+ cells (monocytes) (18.0 +/- 0.6 versus 17.0 +/- 0.4%; p = 0.2), or HLA-DR+ cells (14.5 +/- 0.5 versus 14.0 +/- 0.4%; p = 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)