Infectious complications are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT), and the lung is a particular target organ post-transplant. Our laboratory has used a murine bone marrow transplant model to study alterations in immunity that occur as a result of transplantation. Our studies focus on immune responses that occur following immune cell reconstitution in the absence of immunosuppressive drug therapy or graft-versus-host disease. We have found that impaired clearance of both bacterial and viral pulmonary infections is related to specific alterations in immune cell function and cytokine production. Our data offer insight into mechanisms that contribute to opportunistic infections in HSCT recipients.