A single intracheal dose of liposome-encapsuled dichloro-methylene-diphosphonate resulted in the elimination of alveolar macrophages (AM) from the lung, creating a model to study the in vivo role of AM in the pulmonary immune response. Using intratracheally administered trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), the kinetics of the response, the location and number of TNP-specific antibody-forming cells, and the different Ig classes of the antibodies produced were studied in AM-depleted animals. The results show that AM elimination has a dramatic effect on the pulmonary immune responses against TNP-KLH. An increase in APC in lung-associated lymph nodes and a prolongation of the response is found, as well as an introduction of APC in lung tissue. In both experimental groups, the majority of the TNP-specific antibodies produced was IgG, followed by IgA and IgE, while very few IgM antibodies could be detected. We conclude from these results that AM are likely to play a role in controlling the pulmonary immune response in a suppressive way, thereby limiting the possible damage caused by severe immune responses in lung tissue.