Background. Increases in blood flow support oxygen (O-2) delivery with hemodilution. However, with alpha -stat management, the cerebral response to hemodilution is blunted. We tested the hypothesis that carbon dioxide (CO2) management is a primary determinant of the cerebral blood flow (CBF) response to hemodilution during hypothermic bypass. Methods. Following Animal Care Committee approval, 15 dogs underwent bypass at 18 degreesC (pH-stat, n = 7 or alpha -stat, n = 8). Measurements were obtained after progressive hemodilution, and cerebral blood flow was determined by sagittal sinus outflow. Arterial pressure was maintained at 60 to 70 mm Hg. The CBF response to hemodilution and cerebral metabolic rate were compared in the two groups of animals. Results. In both groups, hemodilution increased CBF. At every hematocrit, CBF and O-2 delivery in the pH-stat, group exceeded that of alpha -stat group, although O-2 demand did not differ between groups. While absolute CBF in the pH-stat group was greater at every hematocrit, the relative change in CBF from control and the slope of the CBF-Hct relationship did not differ between groups. Conclusions. p H-stat management is associated with a greater absolute CBF and a greater ratio of cerebral O-2 supply to demand for any degree of hemodilution. However, over the range of hematocrits common in practice, CO2 management per se does not determine the cerebral response to hemodilution. (C) 2001 by The Society of Thoracic Surgeons.