Lymphocytes in the bronchoalveolar space are routinely obtained and examined in lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes were found in regional lymph nodes after intrabronchial instillation, indicating that reentry of lymphocytes from the bronchoalveaolar space into the body is possible. In the present study, the route and kinetics of the reentry of bronchoalveolar lymphocytes were investigated in a congenic rat model using immunohistochemistry on cryostat and semithin sections and confocal laser scanning microscopy. As early as 15 min after intratracheal instillation lymphocytes were found to leave the bronchoalveolar space by transmigration through alveolar but not bronchial epithelium and were observed in interstitial alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes appeared in the draining lymph nodes of the lung with an increase after 24 and 48 hr. The kinetic pattern clearly differed in nondraining lymph nodes and other organs. After 6 hr, only single cells were found in nondraining lymph nodes, spleen, and blood with a slight increase after 24 hr, and only occasionally were single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after instillation. In conclusion, T and B lymphocytes can leave the alveolar space by reentry into the lung tissue through alveolar epithelium. They reach regional lymph nodes by means of lymphatic vessels and are then distributed all over the body to rejoin the systemic immune system. Coming into contact with environmental antigens, these lymphocytes could perform an important function in the lung immune system and might be a target for inhalative therapy. Anat Rec 264:229–236, 2001. © 2001 Wiley-Liss, Inc.