Perfluorooctylbromide (PFOB) is a perfluorocarbon that has been shown to improve lung function in infants and animals with respiratory distress secondary to surfactant deficiency. We recently demonstrated that although PFOB treatment improved lung function and survival in surfactant protein-B(SP-B) deficient newborn mice, it also adversely affected lung histology. To more closely examine the effects of PFOB on the lung, we instilled PFOB into the lungs of Balb/c mice (n=137, anesthetized with methoxyflurane) in amounts equal to the estimated functional residual capacity. The mice recovered within 1-5 min and were examined 3h-7d after treatment. By 3h, histologic examination revealed evidence of interstitial swelling in perivascular areas and alveolar damage consisting of septal swelling with abundant cells and exudate in the alveoli. Total cells recovered in bronchoalveolar lavage fluid (BAL; sum of 5×1mL washes with cold saline obtained immediately after euthanasia) increased from 2.33±0.70×105 at baseline to 3.85±0.74×106 and 1.42±0.22×107 at 3 and 24 h after treatment, respectively (p<0.0001, ANOVA). The majority of these cells were foamy macrophages (>90% at 3 h) and neutrophils (>40% at 24 h). Lung permeability, assessed by measuring the amount of125 I-albumin injected i.p. that gained access to the lavage fluid after 2 h, increased significantly to 3x baseline at 3h and to 4.4x baseline at 5h following PFOB treatment (p<0.04). Although SP-B concentration remained unchanged in BAL fluid, protein concentration increased significantly(p<0.03) so that the ratio of SP-B to protein concentration decreased significantly (p<0.05) following PFOB treatment. Preliminary measurements of static lung compliance indicate that PFOB treatment alters lung compliance. These studies in mice demonstrate that early effects of PFOB treatment may alter lung structure, integrity and SP-B function in a manner that can seriously affect lung function.