Within the framework of the SAPALDIA survey (Swiss study on Air Pollution and Lung Diseases in Adults), we studied the influence of sex, age and smoking habits on total serum IgE and allergen-specific IgE antibody concentrations (assessed by means of the Phadiatop® test) and on the prevalence of hay fever. A total of 8,344 subjects aged 18–60 years, comprising 2,776 current smokers, 1,888 former smokers and 3,680 nonsmokers, were included in the study. Smokers had both a statistically significant (p < 0.001) higher mean serum IgE concentration (geometric mean 39.7 kU/l), and a higher percentage (27.5%) of persons with elevated serum IgE ( > 100 kU/l) than nonsmokers (27.2 kU/l; respectively 20.5%). The IgE level was significantly lower in women than men (p < 0.001) in all smoking categories. The percentage of persons with positive atopic markers (positive Phadiatop test, positive skin prick tests to common inhalant allergens) and self-reported hay fever was significantly higher in nonsmokers than in smokers or former smokers. In Phadiatop positive (atopic) subjects, the IgE levels were highest, with a mean of 104.3 kU/l (99.0–109.8), and lowest in Phadiatop-negative nonsmokers at 27.2 kU/l (25.9–28.6). These findings correlate well with the current interpretation of total serum IgE values in screening for atopic diseases in adults (IgE < 20 kU/l: atopy improbable; IgE > 100 kU/l: atopy probable). In multivariate logistic regression models, the prevalence of positive Phadiatop tests, positive skin tests, and atopy decreased significantly with age. The odds of having a positive Phadiatop and skin test, or being atopic were found to decrease on average by 23.0, 21.1 and 21.0%, respectively, with every 10-year increase in age. With respect to smoking status, the odds ratios for the three atopic markers were significantly lower in current and former smokers than in non-smokers. The prevalence of (self-reported) hay fever was highest in nonsmokers, intermediate in former smokers (odds ratio = 0.81, p < 0.05) and lowest in current smokers (odds ratio = 0.76 in comparison to former smokers, p < 0.01). The odds ratio of self-reported current hay fever decreased with age at an estimated average of 23% every 10 years. The decrease in former smokers might be slightly faster than in the other two categories. In conclusion, the present results demonstrated that tobacco smoking is associated with increased IgE levels and negatively related to atopy and hay fever. In addition, it is shown that atopy prevalence decreases with age.