The neuroendocrine (NE) system may play an important role in smoking-induced airway diseases. The aim of the present study was to examine the relationship between serum levels of the general NE marker chromogranin A (CgA) and smoking habits, respiratory symptoms and lung function. The study population consisted of never-smokers with normal lung function, smokers with normal lung function and smokers with airway obstruction who were randomly selected from the lung study of the Nord-Trøndelag Health Study (HUNT). Serum CgA was determined in 151, 138 and 116 subjects, respectively. All subjects were seronegative for Helicobacter pylori. Male smokers with airway obstruction had significantly higher serum CgA levels (median 3.70 nmol x L(-1) (interquartile range 3.10-5.15)) than both smokers with normal lung function (3.00 nmol x L(-1) (2.50-3.67)) and never-smokers with normal lung function (2.90 nmol x L(-1) (2.57-3.30)). The elevated levels of CgA correlated with the degree of airway obstruction. Moreover, the presence of respiratory symptoms and chronic bronchitis among male smokers were associated with increased serum CgA levels. Females had CgA levels similar to male smokers independent of smoking status and lung function. Elevated serum chromogranin A levels in subjects with airway obstruction and respiratory symptoms may represent neuroendocrine activation in inflammatory or remodelling processes in the lung.