Summary Background Smoking is a major risk factor for lung diseases and lower respiratory symptoms, but since not all smokers develop chronic bronchitis and since chronic bronchitis is also diagnosed in never-smokers, it has been suggested that some individuals are more susceptible to develop chronic bronchitis due to genetics. Objective To study the relative influence of genetic and environmental factors on the variation in the susceptibility to chronic bronchitis. Methods In a population-based questionnaire study of 13,649 twins, 50–71 years of age, from the Danish Twin Registry, we calculated sex-specific concordance rates and heritability of chronic bronchitis. The response rate was 75%. Results The prevalence of chronic bronchitis was 9.3% among men and 8.5% among women. The concordance rate for chronic bronchitis was higher in monozygotic twins than in dizygotic twins among women; 0.30 vs. 0.17, but not among men; 0.15 vs. 0.18. The heritability of chronic bronchitis adjusted for smoking and age was 55% (36–71%) in women, whereas the susceptibility to chronic bronchitis in men for 25% (8–41%) was ascribable to familial environment but not to genetic factors. Conclusions Chronic bronchitis shows a moderate familial aggregation, particularly in women. Increased susceptibility to respiratory disease among female smokers relative to male smokers may have a genetic origin.