Lesions of respiratory bronchiolitis may be observed involving occasional respiratory bronchioles in lung specimens from cigarette smokers unaccompanied by clinically significant findings. Less frequently, respiratory bronchiolitis may be more extensive and accompanied by clinical and morphologic changes called respiratory bronchiolitis-associated interstitial lung disease (see Chapter 80). Respiratory bronchiolitis consists of collections of lightly pigmented macrophages within the lumens of respiratory bronchioles. The cytoplasm of the macrophages contains finely granular particles that are brown on hematoxylin and eosin and stain faintly with iron stain. This material has been referred to as smoker’s pigment. Collections of similar pigmented macrophages are typically found in the lumens of adjacent alveolar ducts and alveoli and may be seen in the lumens of membranous (terminal) bronchioles as well. The walls of the bronchioles exhibit variable infiltrates of lymphocytes and histiocytes containing the same finely granular pigment as the macrophages and/or coarse black anthracotic pigment. Variable peribronchiolar fibrosis may also be present involving the bronchiolar walls and first tiers of adjacent alveolar septa. The fibrotic alveolar septa may exhibit type 2 pneumocyte hyperplasia or metaplastic bronchiolar epithelium (lambertosis). In some individuals, the respiratory bronchiolitis may be extensive or severe enough to result clinically in diffuse interstitial lung disease called respiratory bronchiolitis-associated interstitial lung disease (see Chapter 80).