Total serum IgE, Phadiatop, and the skin prick test (SPT) are commonly used to diagnose atopic diseases. However, no large study has ever been done to test their diagnostic efficiency. We studied the diagnostic value of these three atopic markers in 8329 well-randomized adults from the Swiss Population Registry. The prevalence of current allergic asthma (CAA) was 1.8% and of current allergic rhinitis (CAR) 16.3%. The prevalences of positive Phadiatop, positive SPT (at least, one out of eight SPT to common aeroallergens with a wheal of > or = 3 mm), and positive total IgE (IgE > or = 100 kU/l) were 29, 23, and 23%, respectively. To diagnose CAA and CAR, the sensitivity of Phadiatop was significantly higher than that of SPT (72.5% vs 65.4%, 77.1% vs 68.4% respectively; P < 0.01 and < 0.001) and IgE (72.5% vs 56.9%, 77.1% vs 43.9%, respectively; both P < 0.001). The sensitivity of SPT was significantly higher (68.4% vs 43.9% P < 0.001) than that of IgE to diagnose CAR. When CAA and CAR were excluded, the SPT specificity was significantly higher than that of Phadiatop (77.8% vs 71.9% and 85.9% vs 80.5%, respectively; both P < 0.001): when CAR was excluded, SPT was significantly higher than IgE (85.9 vs 81.4%; P < 0.001). SPT had significantly the best positive predictive value for CAA (5.2% for SPT vs 4.6% for both IgE and Phadiatop; both P < 0.001) and CAR (48.7% for SPT vs 43.5% for Phadiatop and 31.6% for IgE; both P < 0.001). The three markers of atopy had roughly the same negative predictive value (NPV) for CAA, but IgE had a significantly lower NPV for CAR than SPT and Phadiatop (88.1% vs 93.3% and 94.7%, respectively; both P < 0.001). The diagnostic efficiency of SPT was significantly higher than that of Phadiatop (83.1% vs 79.9% and 77.6 vs 71.9%, respectively; both P < 0.001) to diagnose CAR and CAA. IgE and SPT had equal efficiency (77.6%), which was significantly higher than that of Phadiatop, to diagnose CAA (71.9%; both P < 0.001). In conclusion, SPT have the best positive predictive value and the best efficiency to diagnose respiratory atopic diseases. Furthermore, SPT give information on sensitivity to individual allergens and should therefore be used primarily by clinicians to assess respiratory allergic diseases. Moreover, they are cheaper and provide immediate, educational information for both patient and physician.