A 6-year semiquantitative clinicopathologic study revealed that among 196 men and 46 women 40 or more years of age at death, the severity of destructive emphysema was overwhelmingly the most important morphologic correlate of the clinical state of chronic airway obstruction. The pathogenic mechanisms whereby emphysema may lead to airway obstruction are probably multifactorial, but our data are consistent with a growing consensus that loss of small airway support by surrounding lung tissue in emphysema may cause kinking, tortuosity, and collapse of the airways, with subsequent increased airflow resistance and clinical obstruction. Pathologic changes (inflammation, fibrosis, increased goblet cells, and mucous gland enlargement) in large or small airways in the absence of much emphysema were very seldom associated with significant chronic airway obstruction, and correlated rather poorly with chronic airway obstruction, regardless of severity of emphysema. A subjective method of evaluating mucous gland enlargement in the large airways was consistently better than the Reid Index in correlations with clinical and anatomic abnormalities, presumably because it took all glands into consideration. The clinical features of subjects with severe centrilobular versus severe panlobular emphysema were essentially the same. "Blue bloater" and "pink puffer" clinical types of chronic airway obstruction continued to reveal differences in airway pathologic features, but no longer revealed a major difference in the severity of emphysema at the time of death. Presumably this was due, at least partially, to improved treatment, longer survival, and fusion into a similar end-stage. The total exposure to cigarette smoke was quantitatively related to clinical chronic airway obstruction and to both alveolar and airway pathologic features.