We examined the lungs from 48 autopsied patients in the National Institutes of Health Intermittent Positive-Pressure Breathing trial who had moderately severe and severe chronic airflow obstruction. Compared with control patients without heart or lung disease, IPPB patients had mucous gland enlargement and increased muscle and decreased cartilage in bronchi. Most patients had severe emphysema. The bronchioles were narrower and more irregular in shape than in the control subjects. Bronchiolar inflammation, increased muscle and goblet cell metaplasia were moderately severe. Bronchioles had a higher proportion of muscle in younger control subjects than they did in older control subjects. A wide variation in severity of lesions in bronchi and bronchioles was observed. Correlations between lesions were of relatively low order. Mucous gland enlargement was negatively related to one measurement of emphysema and negatively related to bronchial eosinophilia. Mucous gland enlargement was not related to bronchial or bronchiolar inflammation or to bronchiolar narrowing. Emphysema was associated with decreased central airway muscle, decreased bronchial eosinophilia, increased bronchiolar narrowing, and distortion in the shape of bronchiolar lumens. Interrelationships between bronchiolar lesions were primarily between measurements of dimensions, and there was no relationship between bronchiolar narrowing and bronchiolar inflammation or fibrosis. Bronchiolar muscle was positively related to regularity of bronchiolar shape. We conclude that although lesions in the bronchi and bronchioles and parenchyma (emphysema) are easily demonstrable in patients with moderate and severe chronic air-flow obstruction, they vary widely in severity. The interrelationships are not strong, suggesting that relationships are due to a common etiologic agent, tobacco smoke.(ABSTRACT TRUNCATED AT 250 WORDS)