Alveolar macrophages from guinea-pigs sensitized by different amounts of ovalbumin, administered either by subcutaneous injection or aerosol exposure, liberate increased amounts of arachidonic acid and thromboxanc B2 when challenged in vitro with ovalbumin. This antigen-dependent activation of macrophages was immunospecific. The comparison between different sensitization procedures showed that the aerosol exposure was the most efficient with respect to the activation of macrophages, as cells from guinea-pigs sensitized subcutaneously were poorly activated by the antigen unless high doses were used for sensitization. The antigen-dependent activation of macrophages was affected by acid and neutral washings, suggesting the involvement of a loosely bound antibody that could not be identified. These observations suggest that, as mast cells and basophils, alveolar macrophages from actively sensitized guinea-pigs contribute to the allergic reaction by an antibody-mediated mechanism.