Airflow obstruction and serum immunoglobulin E (IgE) were assessed in 250 men and women 65 to 91 yr of age who had been selected from a larger general population sample according to reported respiratory symptoms. After allowance for age and sex, serum IgE and smoking interacted synergistically as risk factors for airflow obstruction such that on average an IgE > or = 81 IU/ml in current smokers was associated with a FEV1/FVC ratio 14.4 percentage points (95% CI, 8.8 to 19.9) less than in lifelong nonsmokers with an IgE < or = 10 IU/ml. This synergistic interaction was apparent in subjects who showed no evidence of airway lability (i.e., no hyperresponsiveness to inhaled methacholine or, if bronchial hyperresponsiveness could not be tested, no clear improvement in airflow obstruction after inhalation of salbutamol). The findings suggest that the role of IgE in the pathogenesis of airflow obstruction is not confined to asthmatics.