An investigation on the occurrence and role of acute-phase reactants in experimental inhalation lung disease (ILD) was undertaken. Using an experimental model of ILD in which rabbits are exposed to aerosols of appropriate fungal spores, haptoglobin analysis was compared with depressions in arterial oxygen tension (PaO2) with time following challenge. Haptoglobin values of rabbits exposed to single 30-min aerosol challenges of Aspergillus terreus, demonstrated a significant (two- to three fold) increase 24-48 hr after challenge. Haptoglobin elevation was found to be a more reliable and consistent indicator of pulmonary inflammation than depression of PaO2. In an effort to determine the role of haptoglobin in this response, acute phase reactant levels were elevated either actively or passively. When rabbits with augmented haptoglobin levels were exposed to aerosol challenges with A. terreus, the typical depressions in PaO2 at 1-4 hr postchallenge were not observed. This indicated the plasma containing elevated acute-phase reactants may be involved in limiting the pulmonary response that normally occurs following challenge. Haptoglobin was not found to bind to A. terreus spores in vitro.