Airway wall remodeling in asthma and chronic obstructive pulmonary disease (COPD) can have a profound effect on the function of the airways. We tested the hypothesis that airflow obstruction and estimates of peripheral airway inflammation correlate with airway wall thickness and the amount of bronchial smooth muscle in cartilaginous airways. In addition, we estimated the theoretical relation between airway dimensions and airway resistance with a computational model. Lung tissue was obtained from 72 patients with different degrees of COPD who were operated on for a solitary peripheral lung lesion. In 341 transversely cut cartilaginous airway sections we measured airway size and airway wall dimensions. Inflammatory changes from the same lungs were scored in noncartilaginous airways. Preoperatively measured maximum expiratory flows and the response to a bronchodilator were correlated with airway wall dimensions. Maximum expiratory flow, the reversibility of airflow obstruction, and peripheral airway inflammation were significantly related to the airway wall area but not to the smooth muscle area. We conclude that airflow obstruction and its reversibility in COPD is in part caused by thickening of the cartilaginous airway wall and is related to inflammatory changes.