Although capsaicin provocation has been used to evaluate treatment against cough, which is one of the most common respiratory symptoms, there are still methodological considerations that are not fully known. Capsaicin stimulates the unmyelinated slow C-fibres of the sensory nervous system, which leads to coughing. Smoking often leads to respiratory symptoms with cough and phlegm. The aim of this study was to examine the effect of smoking on capsaicin provocation. Subjectively healthy smokers and non-smokers were challenged with capsaicin in increasing doses. The coughs were counted and irritation of the lower airways was graded on a symptom score. Smokers reacted to provocation with significantly fewer coughs, but there was no difference regarding other symptoms. These results are in agreement with the hypothesis that nicotine inhibits or blocks C-fibres of the sensory nervous system of the lower respiratory tract. Clinically, this may serve to explain increasing airway symptoms that are often seen after cessation of smoking.