Arterial-alveolar differences for oxygen, carbon dioxide, and nitrogen were measured in 7 non-distressed preterm infants and 21 ventilator-dependent preterm infants with hyaline membrane disease. The preterm infants with hyaline membrane disease had a significantly lower average arterial pH (7.34 vs. 7.44; P less than 0.001), and significantly higher arterial-alveolar differences for oxygen (286 mm Hg vs. 34 mm Hg; P less than 0.005) and nitrogen (118 mm Hg vs. 7 mm Hg; P less than 0.005). Both groups had elevated arterial-alveolar differences for PCO2 (9 mm Hg in infants with hyaline membrane disease, 5 mm Hg in nondistressed infants; P less than 0.2). When acute changes in mean airway pressure were produced in 14 distressed infants, arterial-alveolar CO2 and N2 differences moved in opposite directions in 11 infants. This observation suggests that changes in mean airway pressure do not acutely recruit atelectatic alveoli, but cause redistribution of ventilation within alveoli already ventilated.