The effects of ECMO on cerebral dynamics, particularly in the face of asphyxia, are largely unknown. We inquired as to whether carotid artery blood flow (CABF) and intracranial pressure (ICP) were affected by carotid artery/jugular vein ligation, asphyxia, ECMO, and ECMO with asphyxia. Lightly sedated newborn lambs (two to four days old, 3 to 4 kg) in four groups were monitored for mean ICP by an epidural sensor, mean CABF by a flow probe, and mean arterial pressure. Mean values were determined for the duration of each step of the experiment. ECMO was venoarterial at 100 to 120 mL/kg/min. CABF and ICP were measured in group 1 before and after CA/JV ligation; in group 2 during normoxia/normocapnia followed by hypoxia (30 to 40 torr)/hypercapnia (70 to 90 torr); in group 3 before, during, after ECMO while normoxic/normocapnic throughout; and in group 4 as ECMO was begun while hypoxic/hypercapnic. Vessel ligation alone caused no significant CABF/ICP changes. Asphyxia caused physiologic increases in CABF (P less than .03) and ICP (P less than .01). ECMO alone caused a significant decrease in ICP (P less than .003). ECMO with asphyxia caused an even more severe decrease in ICP (P less than .001) combined with augmented CABF (P less than .03). The ICP decrease was limited to the duration of ECMO. Possible explanations include loss of cerebral autoregulation induced by hypoxia/hypercarbia and alterations in cerebral venous drainage necessitated by this method of cardiopulmonary bypass.