Seven lambs (0.93 term gestation) were delivered by cesarean section with evidence of meconium in the amniotic fluid, meconium staining, and respiratory distress. The initial arterial blood gas and acid-base status indicated severe hypoxemia and acidosis. Three of these lambs developed pneumothoraces and died on control gas ventilation with positive end expiratory pressure. During the control period (90 min) with ventilatory support, there were no significant alterations in mean arterial oxygen tension (PaO2) and alveolar-arterial oxygen gradient (A-aDO2). The initial hypercarbia and acidosis were effectively controlled and corrected using mechanical ventilation and bicarbonate infusion. Fifteen min after the onset of fluorocarbon ventilation mean PaO2 significantly increased and A-aDo2 decreased. After 90 min of fluorocarbon ventilation, lambs were returned to gas ventilation. During this recovery period, PaO2 and A-aDo2 remained significantly improved compared with control gas values. Dynamic lung compliance increased, alveolar and peak tracheal pressure decreased and inspiratory elastic work of breathing decreased during liquid ventilation.