The diffusion of oxygen across the two sides of the alveolar membrane can be determined by the alveolar surface area, the thickness of the alveolar membrane and the difference of the partial pressure of oxygen across the alveolar and the vascular sides of the membrane. Chronic respiratory morbidity following premature birth is characterised by a decrease in the total alveolar surface area and a thickening of the alveolar membrane, both of which phenomena negatively affect the diffusion of oxygen. The alveolar arterial oxygen gradient can describe the difference in the partial pressure of oxygen across the two sides of the alveolar membrane. This gradient attains low values in health, but can increase to considerably higher values in diseases such as bronchopulmonary dysplasia or congenital diaphragmatic hernia. A normal or increased alveolar arterial gradient can be used in the differential diagnosis of the mechanism of hypoxaemia.