Cough reflex testing with capsaicin has been used to study the pathophysiology of the cough reflex and the antitussive effects of various drugs. Although the reproducibility of capsaicin-induced cough has been well established in normal subjects, it is not known if prior challenge with capsaicin reduces the subsequent cough response to inhaled capsaicin in patients with the sinobronchial syndrome, a condition characterized by chronic upper and lower airway inflammation. Measurement of the capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was repeated four times at intervals of 15, 30 and 60 min in eleven patients with the SBS and ten normal subjects. The cough thresholds at 15, 30 and 60 min were greater than the initial value in patients with the SBS but not in normal subjects. In addition, we examined the effect of 4 days treatment with indomethacin (100 mg/day) on the cough thresholds measured twice at an interval of 15 min in eight patients with the SBS. Indomethacin increased the initial cough threshold and reduced the increment in the post-15 min cough threshold from the initial value compared with placebo, thus reducing the tachyphylaxis. These results indicate that chronic airway inflammation may be responsible for the decreased response (tachyphylaxis) to repeated inhalation of capsaicin, and suggest that cyclooxygenase products released by the airway inflammation may be involved in tachyphylaxis, cough receptor sensitivity to inhaled capsaicin, or both, in patients with the SBS.