In epidemiologic studies of asthma there is a group with recent wheeze, but with no airway hyperresponsiveness (AHR), in whom it is unclear whether any significant airway abnormality exists. Exhaled nitric oxide (NO) has been proposed as a measure of airway inflammation. We measured exhaled NO in a population sample of 306 young adults who also underwent bronchial challenge with histamine or a bronchodilator test. Subjects blew into a 3-L Tedlar bag against a 2-mm-diameter resistance to close the soft palate and exclude nasal air. The NO content of expired gas from a single breath was analyzed by chemiluminescent analyzer. Exhaled NO was log-normally distributed in the population sample and duplicate measurements were highly reproducible (intraclass correlation coefficient = 0.98). Exhaled NO correlated significantly with airway responsiveness, measured as the dose-response ratio to histamine (r = 0.39, p < 0.001) and with peripheral blood eosinophils (r = 0.35, p < 0.001). Exhaled NO was significantly greater in asthmatic subjects (geometric mean, 22.2; 95% confidence intervals, 16.1 to 30. 7 ppb) than in normal subjects (7.8, 7.1 to 8.4, p < 0.001) or in subjects with wheeze but no AHR (8.8, 7.5 to 10.3, p < 0.001). We conclude that exhaled NO is log-normally distributed, is highly reproducible and discriminates well among subjects, suggesting that it is both a feasible and useful measurement for epidemiologic studies of asthma. The findings suggest that wheeze in the absence of AHR is unlikely to be associated with airway inflammation.