To assess the ability of the methacholine challenge test for separation between normals and patients with clinically apparent mild airway hyperreactivity, the provocative dose of inhaled methacholine required to cause a 20% drop in the forced expiratory volume in one second was evaluated in two selected pediatric populations. On the basis of a standardized respiratory questionnaire, 70 subjects, 4-16 years of age were identified. Included were 49 normal individuals, and 21 individuals with mild airway hyperreactivity who responded to bronchodilators. Methacholine inhalation challenges were performed by use of a standard inhalation procedure. Forty-seven percent of the normals (23/49) had a positive methacholine challenge test while 24% (5/21) of the patients with hyperreactive airways had a negative test by the standard criteria. A wide spectrum of specificity and sensitivity of methacholine challenge was obtained at different doses of methacholine. The greater the sensitivity, the lower the specificity. Therefore, we postulate that the methacholine challenge test can be helpful in making the clinical diagnosis but it does not allow a clear and perfect separation between normal and clinically apparent mildly airway reactive patients in a pediatric age population.