SummaryThirty-four Western mixed breed lambs were delivered prematurely at 120 days gestational age (term = 150 days). Four lambs were sacrificed at birth, and four lambs were sacrificed with the onset of respiratory failure (PCO2> 80 torr) at about 30 min of age. The remaining lambs were treated by tracheal instillation with 50 mg of natural sheep surfactant lipid/kg body weight. These lambs were sacrificed 10 min, 40 min, 1.5 h and 3 h after surfactant treatment. Frequent blood gas and compliance measurements documented the clinical responses of the lambs.Lungs from treated lambs showed large increases relative to untreated lungs in air volumes as assessed by pressure-volume curves and by histology. However, the pressure-volume and histologic measurements did not distinguish between the posttreatment groups of lambs. Minimum surface tensions of alveolar washes fell from >30 dynes/cm to 6.3 dynes/cm 10 min after treatment and again rose to 21.6 dynes/cm within 3 h. Minimum surface tensions correlated well with the PO2values but not with the PCO2values measured before sacrifice. The combination of dilated distal airways and atelectasis resulted from increasing surface tensions with time and mechanical ventilation and may explain the clinical deterioration without much change in the volume of gas within the airways.