We determined whether cerebral blood flow (CBF) remained related to arterial O₂ content () during hypoxic hypoxia when hematocrit and hemoglobin concentration were independently varied with cell-free, tetramerically stabilized hemoglobin transfusion. Three groups of pentobarbital sodium-anesthetized cats were studied with graded reductions in arterial O₂saturation to 50%: 1) a control group with a hematocrit of 31 ± 1% (mean ± SE;n = 7);2) an anemia group with a hematocrit of 21 ± 1% that underwent an isovolumic exchange transfusion with an albumin solution (n = 8); and3) a group transfused with an intramolecularly cross-linked hemoglobin solution to decrease hematocrit to 21 ± 1% (n = 10). Total arterial hemoglobin concentration (g/dl) after hemoglobin transfusion (8.8 ± 0.2) was intermediate between that of the control (10.3 ± 0.3) and albumin (7.2 ± 0.4) groups. Forebrain CBF increased after albumin and hemoglobin transfusion at normoxic O₂ tensions to levels attained at equivalent reductions in in the control group during graded hypoxia. Over a wide range of arterial O₂ saturation and sagittal sinus P O 2 , CBF remained greater in the albumin group. When CBF was plotted against for all three groups, a single relationship was formed. Cerebral O₂ transport, O₂ consumption, and fractional O₂ extraction were constant during hypoxia and equivalent among groups. We conclude that CBF remains related to during hypoxemia when hematocrit is reduced with and without proportional reductions in O₂-carrying capacity. Thus O₂ transport to the brain is well regulated at a constant level independently of alterations in hematocrit, hemoglobin concentration, and O₂ saturation.