Alpha 1-protease inhibitor (alpha 1Pi), an acute-phase reactant, is the major inhibitor of neutral proteases causing lung tissue injury, such as elastase. While examining the acute-phase reaction to the nematode parasite Nippostrongylus brasiliensis, we noticed that the alveolar macrophage was closely associated with alpha 1Pi when the larvae were present in the lung. Histologic examination revealed marked edema and hemorrhage with numerous alveolar macrophages that stain intensely for intracellular alpha 1Pi. Isolation of these cells by bronchoalveolar lavage showed the macrophage to be activated. Cultured alveolar macrophages from normal and infected animals synthesized and secreted alpha 1Pi, as revealed by [35S]-methionine incorporation, but the amounts were insignificant compared with that synthesized by hepatocytes. There was, however, no apparent difference in alpha 1Pi synthetic activity between normal and activated macrophages. The presence of demonstrable intracellular alpha 1Pi in the parasite-activated alveolar macrophage likely represents endocytosis as host protease- and/or parasite protease-antiprotease complexes. Although alpha 1Pi is synthesized primarily by hepatocytes, synthesis by alveolar macrophages may provide immediate local protection in the microenvironment of the lung during an acute inflammatory response.