Five neonates with refractory hypoxemia (aortic PO2 less than or equal to 6.7 KPa despite FiO2 = 1 and efficient artificial ventilation) were investigated in order to determine the principal mechanism of hypoxemia. PO2 values were measured (under FiO2 = 1) in a pulmonary vein, the left auricle and the aorta. They were used to distinguish intra-pulmonary shunts from extra-pulmonary shunts (though foramen ovale and/or ductus arteriosus). Simultaneous measurements of PACO2 and PaCO2 were used to assess the percentage of the ventilation output reaching hypoperfused areas. In cases with extra-pulmonary shunt, when this percentage is over 30%, pulmonary hypertension is likely. The use of both methods is useful for selecting those patients who might benefit from tolazoline.