To define whether coughing during mannitol challenge is a nonspecific side effect of this challenge or is associated with asthma. A prospective study. University hospital. Thirty-seven steroid-naive, asthmatic subjects and 10 healthy subjects. The participants completed a symptom questionnaire, recorded peak expiratory flows (PEFs), and underwent spirometry, skin tests, and bronchial provocations with mannitol, histamine, and cold air. Seventeen of the asthmatic subjects were treated with budesonide, 800 micro g per day, and the measurements were repeated after 3 and 6 months of treatment. Coughs were recorded during the mannitol challenges, and the cough sensitivity was expressed as the cumulative number of coughs divided by the cumulative dose of mannitol. The asthmatic subjects coughed more during the mannitol challenge than the healthy subjects (8.3 coughs per 100 mg [95% confidence interval (CI), 6.2 to 11.0] vs 1.1 coughs per 100 mg [95% CI, 0.4 to 3.0]; p < 0.0001). Even those asthmatic subjects who did not develop bronchoconstriction after the maximal cumulative dose of mannitol (635 mg) coughed significantly more than the healthy subjects (53 coughs [95% CI, 34 to 72] vs 12 coughs [95% CI, 4 to 21]; p = 0.003). Budesonide treatment decreased the cough sensitivity (p = 0.023), which was significantly associated with improvements in overall symptom frequency, cough frequency, diurnal PEF variation, FEV(1), and bronchial hyperresponsiveness. Coughing during mannitol challenge is associated with asthma and occurs independently of bronchoconstriction. It can be used to study the mechanisms of asthmatic cough. Furthermore, the measurement of the mannitol-provoked coughing may be useful both in the diagnosis of asthma as well as in the assessment of the effects of an anti-inflammatory therapy on this common disorder.