Pulmonary fibrosis and emphysema were produced in beagle dogs by their direct inhalation of cigarette smoke over a relatively short period of time (2-7 cigarettes daily for 2-4 months). One dog was sacrificed after having smoked 172 cigarettes, one after 282 cigarettes, and the others after 480 and 534 cigarettes, respectively. Examination of the lungs by scanning and transmission electron microscopy showed a range of response from the presence of numerous smoker's macrophages to extensive alterations, including destruction and enlargement of alveolar ducts and varying degrees of enlargement of alveolar spaces. Interalveolar pores were enlarged, and marked fenestration leading to destruction of the alveolar walls became apparent. These features were accompanied by interstitial fibrosis of the interalveolar septa. Light-and electron-microscopic examination showed no evidence of bronchitis and/or bronchiolitis or of physical obstruction to the terminal airways in the early development of fibrosis and emphysema.