Background: Many studies have shown that cigarette smoking is associated with elevated concentrations of total serum IgE. Few studies, however, have examined total IgE in relation to passive smoking exposure, especially in adults. This cross-sectional study investigated the association of active and passive smoking exposure with levels of total serum IgE in Japan. Methods: Study subjects were 981 pregnant women in Osaka. Total IgE levels were measured using UniCAP 1000 and were defined as elevated if they exceeded 170 ml/UI. Age, gestation, parity, family history of asthma, atopic eczema and allergic rhinitis, indoor domestic pets, family income, education and the mite allergen level in house dust were selected as potential confounding factors. Results: Current smoking of at least 15 cigarettes a day and 8.0 or more pack-years of smoking were independently related to an increased prevalence of elevated total serum IgE (adjusted odds ratios 3.40 and 2.51, 95% confidence intervals 2.12–5.47 and 1.55–4.06, respectively), and both cigarette smoking status and pack-years of smoking were significantly positively associated with total serum IgE levels, especially in subjects with a positive familial allergic history. There was no measurable association of exposure to environmental tobacco smoke (ETS) at home or at work with total serum IgE concentrations among those who had never smoked. Conclusions: Our results corroborate a positive relationship between active smoking and total serum IgE levels; however, this study failed to substantiate a positive association of ETS exposure with total IgE. Investigations with more precise and detailed exposure measurements are warranted.