The hallmark of sensory hyperreactivity is an enhanced capsaicin induced cough reflex. The cough reflex can be modified by activation of nociceptive (capsaicin-sensitive) nerve terminals. The aim of our study was to assess the influence of exposure to CO(2) concentrations up to 2.0 vol% on capsaicin induced cough reflex on four different occasions. Sixteen healthy volunteers were exposed to CO(2) concentrations of 0.5, 1.0, and 2.0 vol% for 4 h and to clean air in a repeated measures cross-over design. After exposure the capsaicin induced cough reflex was assessed by the single breath dose-response method according to ERS 2007 guidelines. After blank solutions, capsaicin doses (n=12, range 0.49 to 1000 μM) were administrated from a nebulizer combined with a provocation system (Masterscope, software APS version 5.02). Doses were doubled every minute and the concentration causing five or more coughs (C5) was fixed as the end point. The inter-individual C5 capsaicin responsiveness reflected a representative range (0.95-1000 μM). On an intra-individual basis, a good reproducibility could be demonstrated for four tests within 3 weeks. There was no influence of CO(2) challenge on the cough reflex. The first capsaicin test demonstrated a lower C5 threshold independent of the CO(2) concentration applied. In conclusion, assessing the capsaicin cough reflex by single breath inhalation is reliable. However, the at cough sensitivity might be overestimated at the first test occasion. Exposure to CO(2) in concentrations of up to 2.0 vol% has no effect on sensory reactivity.