Since alveolar macrophages (AM) contain large amounts of antioxidants, we hypothesized that AM may be effective scavengers of H2O2 and reduce H2O2-mediated injury. We found that addition of AM to perfusates decreased lung weight gain in isolated rat lungs perfused with the H2O2-generating system of beta-D-glucose and glucose oxidase (G/GO) and that AM were as effective as the addition of erythrocytes or catalase in reducing injury. The ability of AM to protect isolated lungs corresponded with their ability to reduce H2O2 concentrations in vitro. By comparison, azide-treated AM had decreased catalase activity, did not prevent injury to lungs perfused with G/GO, and ineffectively decreased H2O2 in vitro. Mechanical disruption or stimulation of AM by phorbol myristate acetate or zymosan did not alter the AM H2O2-scavenging ability. We conclude that AM can scavenge H2O2 and limit oxidant-mediated injury.