Objective: Conventional mechanical ventilatory support (CV) contributes to lung injury in premature lambs with respiratory distress syndrome, a disease that is characterized by progressive deterioration of gas exchange and increased lung inflammation, Lung recruitment strategies, such as high-frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV), improve gas exchange and attenuate lung inflammation when instituted immediately after birth. However, whether these recruitment strategies are effective as rescue treatment after established lung injury is unknown. To determine the separate and combined effects of HFOV and PLV when initiated after the establishment of acute lung injury in severe respiratory distress syndrome, we studied the effects of these strategies on gas exchange and histologic signs of acute lung injury in premature lambs. Design: Animals were intubated, treated with surfactant and ventilated with 1.00 F10(2) for 4 hrs, After 2 hrs, animals were either continued on CV (controls) or treated with one of three strategies: HFOV; CV + PLV; or HFOV + PLV, The response to low-dose inhaled nitric oxide (5 ppm) was measured in each group at the end of the study. Setting: An animal laboratory affiliated with University of Colorado School of Medicine, Subjects: A total of 20 premature lambs at 115-118 days of gestation (term = 147 days). Measurements and Main Results: In comparison with control animals, each of the rescue therapies improved Pao(2) after 1 hr of treatment. The HFOV and HFOV + PLV groups had higher pao(2) than CV + PLV or CV alone (p < .05), Mean airway pressure (Paw) was lower in the PLV groups during CV or HFOV compared with their controls (p < .05), Inhaled NO improved Pao(2) in all groups; however, the increase in Pao(2) was greatest in the HFOV + PLV group (p < .05), Histologic examination and myeloperoxidase assay were not different between groups, Conclusion: We conclude that each lung recruitment strategy improved oxygenation in premature lambs with established lung injury.