Smoke-induced airway abnormalities are a common feature of the lungs of cigarette smokers. We examined the small airways from guinea pigs exposed to cigarette smoke for periods of 1, 3, 6, and 12 months, and compared these data to those obtained from age-matched, nonexposed animals. We found that there was no change in the structure of the airway walls, and that similar numbers of peribronchiolar alveolar attachments were present in both groups. However, the airway epithelium of animals exposed to smoke for 3, 6, and 12 months had greater numbers of secretory cells/mm length basement membrane. We conclude that this guinea pig model of cigarette smoke-induced lung disease mimics the human condition in that there is alteration of the cellular population of the small airway epithelium. However, the lack of structural changes in the airway wall, with no evidence of peribronchiolar alveolar destruction, suggests that the airflow obstruction seen in these animals is most likely due to emphysematous parenchymal destruction with loss of elastic recoil.