OBJECTIVE To determine whether reactive oxygen metabolite production by alveolar macrophages is affected by liquid perfluorochemical exposure. METHODS Controlled, animal laboratory investigation of alveolar macrophage function in vitro. METHODS Animal research facility of a health sciences university. METHODS Six adult male New Zealand white rabbits and six young piglets. METHODS Alveolar macrophages were obtained after sacrifice from both species by total lung lavage. Macrophages were divided into control and experimental groups. Macrophages in the experimental groups were exposed to perfluorooctylbromide. To determine production of reactive oxygen metabolites, hydrogen peroxide production and chemiluminescence were measured in both experimental and control groups after chemical stimulation. RESULTS Perfluorooctylbromide-exposed alveolar macrophages produced significantly less hydrogen peroxide (1.4 +/- 1.5 vs. 2.4 +/- 1.6 nmol/10(6) cells; p = .002). Perfluorooctylbromide-exposed alveolar macrophages demonstrated significantly less chemiluminescence activity compared with nonexposed cells (0.70 +/- 0.2 vs. 1.5 +/- 0.2 mV of relative activity per 3.5 x 10(5) cells; p = .005). CONCLUSIONS Exposure of alveolar macrophages to perfluorooctylbromide in vitro decreases the responsiveness of macrophages to potent stimuli. This finding may partially explain the decrease in pulmonary inflammation seen in animals treated with partial liquid ventilation during experimentally induced lung injury.