A transplanted lung contains a full complement of immunocompetent lymphocytes and macrophages that are able to react immunologically with recipient lymphocytes and macrophages. In this study, the origin of lymphocytes and macrophages recovered from sequential bronchoalveolar lavages of six heart-lung transplantation recipients was determined by histocompatibility phenotyping. We found that during the first four weeks after transplantation there is a rapid replacement of the donor cells with those of the recipient. Since lung rejection rarely occurs after this transition is complete, donor lymphocytes and macrophages may be an important component of the rejection process. Furthermore, the transition from donor to recipient phenotype indicates that the vast majority of human alveolar macrophages originate from bone marrow precursors.