Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions that make definitive morphological comparisons difficult. Asthma may be divided into extrinsic (allergic), intrinsic (late onset), and occupational forms. The airways in fatal asthma are occluded by markedly tenacious plugs of exudate and mucus; there is fragility of airway surface epithelium, thickening of the reticular basement membrane, and bronchial vessel dilatation, congestion, and edema. There is enlargement of bronchial smooth muscle and also of submucosal gland mass, particularly in medium-sized bronchi. There is increased inflammatory infiltrate comprising activated lymphocytes and eosinophils with release of granular content in the latter; the allergic inflammation is associated with gene expression for interleukins IL-4 and IL-5 (ie, TH2 phenotype) and also GMCSF and TNF alpha. Many of these changes are already present in mild forms of asthma. In comparison, three conditions contribute to COPD: (1) In chronic bronchitis there is inflammation associated with mucous hypersecretion, enlargement of tracheo-bronchial submucosal glands, and a disproportionate increase of acidic mucus. The reticular basement membrane is not consistently thickened. (2) In small (peripheral) airways disease there is a macrophage bronchiolitis, mucous metaplasia and hyperplasia, increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses. Respiratory bronchiolitis and loss of alveolar wall attachments are important lesions. (3) Emphysema involves elastolytic destruction of the alveolar wall; its overall severity, rather than type, appears to be an important determinant of chronic irreversible deterioration of airflow in COPD.