The aim of this study was to assess the impact of surfactant deficiency on the pathophysiology of congenital diaphragmatic hernia (CDH). Pregnant ewes were operated on at 80 days of gestation for creation of a diaphragmatic hernia in the lambs. Twenty-one lambs survived to be delivered by cesarean section and were studied. Compliance was improved when surface tension effects were removed by saline solution in lungs of both control animals and lambs with CDH; however, the lungs of the lambs with CDH still had significantly impaired compliance. In a second series of experiments, two groups were studied: a surfactant-treated and a control, nontreated group. Surfactant was given prophylactically into the liquid-filled lungs before the first breath. All lambs were paralyzed and sedated and their lungs mechanically ventilated with 100% oxygen for 30 minutes; gas exchange was then assessed, pressure-volume data were obtained, and compliance was calculated. Surfactant significantly improved gas exchange; arterial oxygen pressure increased from 39 +/- 11.4 to 316 +/- 53.6 mm Hg, arterial carbon dioxide pressure decreased from 148 to 63 mm Hg, and pH increased from 6.87 to 7.16 (p < 0.001). Lung volume at 25 cm H2O, functional residual capacity, and compliance were all increased (p < 0.02). Thus, in the CDH lamb model, pulmonary mechanics are impaired by both parenchymal and surfactant abnormalities. Both lung mechanics and gas exchange are markedly improved by exogenous surfactant therapy.