The effect of cardiopulmonary bypass on the relationship between brain glucose consumption and regional blood flow is unknown. We measured this relationship in pigs subjected to 3 hours of pulsatile or nonpulsatile cardiopulmonary bypass at normothermia and compared the results to the relationship established in a control group of pigs. A total of 10 regions were sampled in both hemispheres of the porcine brain. In control pigs, cerebral blood flow averaged 46 ml/100 gm and the glucose consumption, 21 mumol/100 gm/min. The ratio between blood flow and glucose consumption was close to 2 ml/mumol in all regions. In pulsatile cardiopulmonary bypass both the whole-brain average and the regional values declined, so that the ratio remained the same, about 2 ml/mumol. In nonpulsatile cardiopulmonary bypass regional blood flow remained normal; the average was 49 ml/100 gm/min, whereas the average glucose consumption declined to 16 mumol/100 gm. In regions with high blood flow rates, the ratio between blood flow and glucose consumption increased to about 3 ml/mumol, indicating perfusion in excess of metabolic demand. We conclude that nonpulsatile cardiopulmonary bypass at normothermia affects the metabolic flow regulation in the brain by interfering with the myogenic contractility of cerebral arterioles.