Some have suggested that tobacco smoke may skew the immune system toward a Th2 pattern, however the effects of genetics or childhood exposures could explain these results. We compared PMBC supernatant or serum Th1 (INF-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokine and IgE levels in members of 45 pairs of nonasthmatic monozygotic twins with varying levels of current cigarette consumption to determine if smoking was associated with Th1/Th2 function after accounting for genetic factors. A statistically significant dose-response was observed between levels of smoking and IL-13 (p=0.05). Mean IL-13 level among heavy smokers (20+ cigarettes/day) was 146% higher than that among nonsmokers (+26.2 pg/mL; p=0.04). The mean IL-5 level among heavy smokers was 166% higher than that among light (<20 cigarettes/day) smokers (+3.4 pg/mL; p=0.03). No statistically significant differences in INF-gamma, IL-4, or IgE levels were observed. Smoking appears to be associated with increased levels of IL-13.