Infection is a major complication of organ transplantation, and the lung is the most common site in recipients of a pulmonary allograft. The generation of an immune response both systemically and in the lungs is a major line of defense against infection. Therefore, we examined the ability of blood monocytes (BM) and alveolar macrophages (AM) recovered from lung transplant recipients without evidence of infection or rejection and from normal subjects to act as accessory cells in mitogen- and antigen-induced proliferation of autologous lymphocytes (Ly) and to stimulate an allogeneic (MLR) and autologous mixed lymphocyte reaction (AMLR). Proliferation of autologous Ly in the presence of mitogen and antigen and of allogeneic Ly stimulated by BM was significantly reduced in the lung recipients when compared with those in the normal subjects. Impaired Ly proliferation may result from inadequate presentation of antigen by recipient BM, heightened suppressive activity of BM, or the inability of recipient Ly to respond to proliferative signals. We believe that our results strongly support a role for inadequate presentation of antigen by BM. Inadequate antigen-driven stimulation could be one reason why transplant recipients have an increased susceptibility to infection. Somewhat unexpected was the finding that AM from lung recipients functioned nearly as well as AM from normal subjects as accessory cells. Although they failed to support mitogen-induced stimulation normally, AM from lung recipients were as efficient as autologous BM and AM from normal subjects in supporting Ly proliferation for soluble antigen and alloantigen.(ABSTRACT TRUNCATED AT 250 WORDS)