Background: Exhaled nitric oxide (eNO) has shown good validity for the assessment of airway inflammation in asthmatic children. In large-scale epidemiological studies, this method would be preferred above airway challenge tests, because it is a quick and easy applicable tool. Objective: In this study, we aimed to assess the discriminatory capacity of eNO, and prechallenge FEV1 for airway hyper-responsiveness (AHR) in 8-13-year old schoolchildren. Materials and methods: Parents completed the ISAAC questionnaire, and children were tested for atopy, AHR to hypertonic (4.5%) saline (HS), and eNO. Diagnostic value was assessed by the area under the receiver operating curves (ROC), and calculation of positive and negative predicted values at different cut-off points for eNO and prechallenge FEV1. Results: Areas under the ROC-curves of AHR were 0.65 for eNO and 0.62 for FEV1. Values increased to 0.71 and respectively 0.75 for a combined occurrence of AHR and current wheeze. Highest sensitivity and specificity were obtained at a cut-off value of 43 ppb for eNO and 103% predicted for FEV1. At these cut-off values, the positive predictive values for the presence of AHR in symptomatic children were respectively 83% (eNO) and 33% (FEV1), and negative predictive values in asymptomatic children were, respectively, 90 (eNO) and 80% (FEV1). Conclusion: Exhaled nitric oxide is a valid screening tool for AHR to HS in children that present with current wheeze, and it outperforms FEV1 as a predictor of AHR.