To verify the optimal hematocrit (Hct) level in the treatment of cerebral ischemia, cerebral oxygen transport (CTO2) and cerebral oxygen metabolism (CMRO2) in graded isovolemic hemodilution were evaluated during cerebral ischemia. Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h after global cerebral ischemia. Global ischemia of the animals was produced by multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood flow (CBF) was measured with radioisotope labeled microspheres. CTO2, CMRO2, and oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen content (CaO2), and venous oxygen content (CvO2). In dogs with global cerebral ischemia, CBF increased with graded isovolemic hemodilution (r=-0.73, P<0.05). CTO2 reached its highest value at a Hct level of 31.3%. CTO2 at Hct of 36.1% and 31.3% was statistically different from the value measured at a Hct of 43.3%, and there was a decrease when Hct was lowered to 25.9%. CMRO2 was the highest when Hct was at 31.3% and differed significantly from the value measured at a Hct of 43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change was not statistically significant compared with the OEF at Hct of 36.1% and 31.3%, respectively. These findings indicate that CTO2 and CMRO2 were the highest when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for cerebral metabolism in ischemic status. Uncoupling of CTO2, CMRO2 with CaO2 was also observed in this study. This phenomenon suggests that hemodilution to augment cerebral circulation may be at least partially attributed to the beneficial effects of hemorheologic improvement in the microcirculation of the ischemic brain.