Allergic sensitization mediated by immunoglobulin E (IgE) is the basis of allergic diseases, and elevated total IgE, in spite of some well-known limitations, is frequently included as a diagnostic criterion for allergic diseases. The reference value of total IgE (IgE-t) in the literature (1.5-144 kU/l) was established almost 2 decades ago. The aim of this study was to establish IgE-t reference values, establishing an updated cutoff value able to identify atopic subjects, defined as a positive CAP-radioallergosorbent test to at least one of a panel of common allergens, among young European adults. The study included 6,670 subjects from 10 Western European countries within the framework of the European Community Respiratory Health Survey II. IgE-t and specific IgE (IgE-s) were measured for the main inhalant allergens; IgE-s in class 0 for all allergens (66.2%) characterized non-atopy. The reference values were estimated by means of linear regression using a 50% random subsample of non-atopic subjects. Two non-atopic subsamples were examined so that one subsample could be used to establish reference IgE-t values, and these values were compared to those in the second non-atopic subsample to validate the findings. Sensitivity and specificity for atopy were assessed on the other 50% of non-atopic and on all atopic subjects. The 95th percentile of IgE-t reference values in non-smokers was 148 kU/l in women and 169 kU/l in men, while it was 194 and 220 kU/l in female and male smokers, respectively: serum IgE-t above the 95th percentile identifies <32% and above the 99th percentile <20% of atopic adults (low sensitivity), but a serum IgE-t below the 95th percentile identifies >90% and below the 99th percentile identifies >95% of non-atopic adults (good specificity). Due to the adequate specificity, IgE-t values exceeding the normal limits confirm a suspected atopic status; however, because of the low sensitivity, values below the cutoff seem not to exclude an atopic status with sufficient accuracy.