Because infection and rejection are the principal complications of any transplant procedure and because the alveolar macrophage is crucial to the defense of the lung from infection and may play a role in lung allograft rejection, we have begun to assess functions of this cell that are thought to be important in lung defense from infection and in transplant immunity. Antimicrobial functions include chemotaxis, which is a mechanism for recruiting macrophages to sites of inflammation and phagocytosis, and intracellular killing of microorganisms. As an accessory cell, the alveolar macrophage is necessary for an effective immune response to develop against either microorganisms or transplantation antigens. Our results indicate that the chemotactic, phagocytic but not the killing capability of alveolar macrophages from lung recipients is impaired. Alveolar macrophages and blood monocytes from lung recipients are also significantly impaired in their support for mitogen and antigen presentation to lymphocytes. Thus, the generation of an effective immune response to a microorganism may be impaired. Alveolar macrophages from lung recipients, however, function as well as those from normal subjects in stimulating lymphocyte proliferation in response to donor antigens (primed lymphocyte test) or unrelated allogeneic antigens (mixed lymphocyte reaction), while their respective blood monocytes function poorly in this regard. Our conclusions are that the antimicrobial functions of the alveolar macrophages are impaired after lung transplantation and this may be one mechanism to explain the unusual susceptibility of the lung allograft to infection. Those functions related to transplant immunity, however, are preserved and indicate that the alveolar macrophage may play a role in allograft rejection.