The mechanism of hemodilution-induced increases in cerebral blood flow (CBF) was investigated. Hemodilution was achieved with a molecular hemoglobin solution (DCLHb) and albumin which have similar viscosities but different oxygen carrying capacities. Part A: CBF was assessed in rats after one of the following regimens: (1) control-hematocrit not manipulated, (2) 30/Alb-hematocrit decreased to 30% with albumin, (3) 30/DCLHb-hematocrit decreased to 30% with DCLHb, or (4) 16/Alb/DCLHb-hematocrit decreased to 30% with albumin and then 16% with DCLHb. For viscosity matched groups (30/Alb and 30/DCLHb), CBF was greater in animals with decreased oxygen content (30/Alb); white in oxygen content matched groups (30/Alb and 16/Alb/DCLHb), CBF was greater in animals with decreased viscosity (16/Alb/DCLHb) (p < 0.05). Part B: Middle cerebral artery occlusion was performed, hemodilution achieved as in Part A, and CBF determined. For viscosity matched groups (30/Alb and 30/DCLHb), CBF was less in rats with decreased oxygen content (30/Alb); while in oxygen content matched groups (30/Alb and 16/Alb/DCLHb), CBF was greater in animals with decreased viscosity (16/Alb/DCLHb) (p < 0.05). This data supports the premise, that in normal brain, both viscosity and oxygen content effect CBF; while in ischemic brain, a decrease in viscosity but not oxygen content increases CBF.