To evaluate sensitivity and specificity of a 4.5% hypertonic saline challenge for a diagnosis of asthma, we studied 393 schoolchildren (13 to 15 yr of age) with "current wheeze," "former wheeze," and without history of wheeze in a community-based, cross-sectional survey. These children were selected from 2.836 schoolchildren in 26 schools in greater Melbourne, Australia who completed a self-administered questionnaire on respiratory symptoms, allergic rhinitis, and eczema. Three hundred eighty-two of 393 children successfully completed a 4.5% hypertonic saline challenge with increasing inhalation periods, and 365 of 393 performed a 6-min standardized, free running exercise challenge. The prevalence of bronchial hyperresponsiveness to hypertonic saline was 20.4%. Sensitivity and specificity for the hypertonic saline challenge to identify children with "current wheeze" were 47% and 92% respectively and for the exercise challenge, 46% and 88%. The agreement of response to hypertonic saline and to exercise was only moderate (kappa = 0.43). Factors associated with increased response to hypertonic saline in a multivariate logistic regression model were a history of "current wheeze," hay fever, response to the exercise challenge, female sex, and a lower baseline predicted FEV1. These results suggest that a 4.5% hypertonic saline challenge shows sensitivity and specificity similar to a standardized exercise challenge and pharmacologic challenges and a higher sensitivity than cold air hyperventilation and distilled water to identify asthma in children in a field study. Measurement of responsiveness to hypertonic saline may be of value as an objective marker of asthma to compare prevalence studies of bronchial hyperresponsiveness and of asthma over time and between countries.