Lung and heart-lung transplantation are effective treatments for many diseases unresponsive to other therapy. However, long-term survival of recipients is limited by the development of obliterative bronchiolitis (OB). In this study, microarray analysis of a heterotopic mouse model of obliterative airway disease (OAD) was used to test the hypothesis that the expression and patterns of genes will correlate with specific changes in tracheal tissue developing a response to allotransplantation and the infiltrating cells manifesting these changes. Expression profiles observed were in accordance with the current paradigm of a predictable sequence of events, beginning with airway injury; an innate immune response followed by an adaptive immune response, including both cell-mediated and humoral components; and eventual loss of airway epithelial cells. These observations confirm and expand the list of genes and molecular processes that can be studied as potential surrogate markers or targets for intervention of OB.