Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection.