The effects of long-term cigarette smoke inhalation on the morphologic and functional integrity of lungs of C57BL/6 young and old mice have been assessed. Smoke exposure occurred over a 9-month period beginning when the young animals were 2 months of age and the old mice 8-10 months. At the termination of the experiment, microscopic and morphometric evaluation of pulmonary tissue revealed peribronchiolar and perivascular accumulations of lymphocytes and macrophages in lungs of both young and old smoke-exposed mice. Such lesions were never observed in sham-treated or control animals of either age. These observations indicate that lesions in mice can be induced by long-term smoke inhalation. In addition, three other anomalous manifestations, prominent only in the smoke-exposed old animals, were noted: 1) reduction of alveolar space with a concomitant increase in lung cellularity and thickened alveolar septa; 2) intra-alveolar accumulation of surfactantlike material; and 3) decreased pulmonary function. Since these abnormalities were prominent only in smoke-exposed old animals, an interaction between smoke inhalation and aging is indicated. Pulmonary function data complement morphologic and morphometric observations and indicate that the manifestation of abnormality noted in the old smoke-exposed animals are restrictive in nature and conform most closely to pulmonary fibrosis.