Despite the established role of cigarette smoking in the causation of chronic air-flow obstruction (CAO), only a small proportion of regular cigarette smokers develop significant clinical disease. We compared emphysema severity as well as pathologic and morphometric features of the peripheral conducting airways and the muscular pulmonary arteries among 3 groups of older subjects. These groups included lifelong nonsmokers (NSM), regular smokers without severe disease (SM), and smokers with an established diagnosis of CAO (SM-CAO). For most pathologic features examined there was an orderly progression in severity when comparing SM to NSM and SM-CAO to SM. Emphysema severity and scores for peripheral airways disease, except for goblet cell metaplasia, better distinguished SM-CAO from SM than did measures of bronchiole lumenal caliber. Within the SM-CAO group, the premortem percent predicted forced expiratory volume in one second (FEV1) correlated significantly with emphysema severity (r = 0.74), with average bronchiole diameter (r = 0.54), with the proportion of bronchioles with diameters less than 400 mu (r = 0.51), but not with any of the scores for bronchiolar disease. However, within this group no morphologic or pathologic feature of the small airways was an independent predictor of ventilatory function beyond that of emphysema alone. When compared with those from NSM, histological sections from SM-CAO lungs contained approximately twice as many fully muscularized artery profiles 0 to 300 mu in diameter, the arterial medial muscle layer was doubled in thickness, and the amount of arterial intimal fibrosis was tripled.(ABSTRACT TRUNCATED AT 250 WORDS)