A single intratracheal instillation of liposomes containing dichloro methylene diphosphonate into rats eliminated > 80% of the alveolar macrophage (AMϕ) population, and the population was not significantly renewed during the ensuing week. AMϕ depletion markedly increased local antibody production in the lung wall in pre‐primed animals exposed to antigen aerosols. However, AMϕ depletion did not affect the normal development of protective tolerance (particularly in the IgE antibody class) to inhaled antigen in immunologically naive rats. These results are discussed in relation to regional control of immune responses in the upper vs. the lower respiratory tract.