Objective: Recently, extracorporeal life support (ECLS) by venoarterial bypass perfusion has been recommended for the treatment of refractory respiratory and/or cardiac failure but the safety of this application for the brain is not yet established. Therefore, the effects of normothermic ECLS on cerebral blood flow, metabolism and electrophysiology were studied in cats with total arrest of cardiopulmonary circulation. Design: An extracorporeal circulation (ECC) system, consisting of a roller pump, a membrane oxygenator and a heat exchanger, was connected to the circulation of cat by cannulae inserted via the jugular vein and femoral vessels. After 2 h ECLS brains were frozen in situ and investigated for changes in regional metabolism. Measurements and results: During 2 h ECC hematocrit declined from 37 +/- 7% to 21 +/- 10% (means +/- SD, p < 0.05), cerebral blood flow decreased to 73 +/- 14% of control (p < 0.05) and cerebral oxygen delivery to 46 +/- 13% of control (p < 0.05) although arterial blood pressure and bypass flow rate did not change. Plasma lactate increased from 0.8 +/- 0.3 to 9.2 +/- 4.2 mumol/ml (p < 0.05), and brain tissue lactate from 2.3 +/- 0.9 to 10.6 +/- 2.7 mumol/g (p < 0.05). Hematocrit correlated positively with cerebral oxygen delivery (r = 0.86, p < 0.001). Conclusions: These data demonstrate that ECLS is associated with reduced cerebral oxygen delivery and may cause brain hypoxia despite normal blood pressure. This complication may contribute to the high incidence of neurological disturbances after prolonged ECLS.