In this study we aimed to assess whether the association between asthma (defined by symptoms and bronchial responsiveness) and total immunoglobulin E (IgE) levels was independent of specific IgE levels to common aeroallergens. A general population-based sample, supplemented with symptomatic individuals, comprising 1,916 young adults, aged 20-44 years, from five areas of Spain, performed a face-to-face respiratory questionnaire, and spirometry, and had total and specific serum IgE levels to mites, pets and moulds recorded. In 1,626 of the subjects, a dose-response methacholine challenge test was completed. Subjects reporting current attacks of asthma showed an association with total IgE (odds ratio (OR) for IgE > 100 kU.L-1 = 4.73, 95% confidence intervals (95% CI) = 2.01-11.12, adjusted for specific IgE, sex, age, smoking, forced expiratory volume in one second (FEV1), and area), which did not vary by bronchial responsiveness. The association between total IgE and asthma also occurred among those with negative specific IgE antibodies (OR 18.0; 95% CI 13.9-120). Individuals with current wheezing and bronchial responsiveness without attacks of asthma also showed an adjusted association with total IgE (OR 4.96; 95% CI 2.32-10.6), which remained for persons without specific IgE (OR 5.86; 95% CI 2.18-1.7). These findings reinforce previous evidence that asthma is associated with increased levels of total IgE, even in subjects negative for specific IgE to common aeroallergens.