The tussive agent capsaicin has achieved common usage in clinical research because it induces cough in a safe, dose-dependent, and reproducible manner. However, the reproducibility of capsaicin challenge testing has been demonstrated only in the short term (study intervals of 20 min to 14 days). In the present study, evaluation of data from several hundred cough challenges performed in the author's laboratory yielded two groups of 40 subjects. In the short-term reproducibility group, subjects underwent cough challenge at an interval of 14 days. Subjects in the long-term reproducibility group were challenged at intervals of at least 6 months (mean 16.7+/-2.4 months, range 6-62 months). All subjects were healthy adult volunteers who underwent identical cough challenge testing, which involved inhalation of incremental, doubling concentrations (microM) of capsaicin until the concentrations inducing two or more (C(2)) and five or more coughs (C(5)) were reached. Results were evaluated in terms of the percentage of subjects whose repeat studies yielded C(2) and C(5) values within one and two doubling concentrations of the initial values. Overall, reproducibility was quite good, with 90-100% of challenges yielding C(2) and C(5) values within two doubling concentrations. Short-term reproducibility of C(5) was superior to that of C(2), suggesting that C(5) is the preferred end point for trials involving serial cough challenges performed within a 14-day period.