The lungs of young smokers and controls of comparable age from a population of sudden non-hospital deaths were systematically studied to determine the relation between cigarette smoking and pathologic changes in peripheral airways. The characteristic lesion observed was a respiratory bronchiolitis associated with clusters of pigmented alveolar macrophages and was present in the lungs of all smokers studied but rarely seen in nonsmokers (p<0.002). The lungs of smokers also showed small but significant increases in mural inflammatory cells and denuded epithelium in the membranous bronchioles as compared to controls (p<0.05). We postulate that this respiratory bronchiolitis is a precursor of centriacinar emphysema and may be responsible for the subtle functional abnormalities observed in young smokers. (N Engl J Med 291: 755–758, 1974)