Data from the neurosurgical critical care arena demonstrate a correlation between cerebral oxygenation, survival, and cognitive function. Transfusion may increase and hemodilution decrease cerebral oxygenation. Both acute and chronic anemia have been associated with cognitive dysfunction. Aggressive blood conservation protocols have been instituted across all age groups without conclusive evidence for their impact upon outcome. Aged subjects are at the greatest risk of cognitive sequelae after major surgery associated with significant blood loss. We hypothesize that cerebral physiologic changes associated with "normal" aging may compromise cerebral oxygenation in the presence of severe anemia.Fischer 344 rats, the NIH National Institute of Aging normal aging rat model, underwent a stepwise isovolemic hemodilution protocol. Age groups (Age Grp) studied were as follows: Age Grp-A (3 months), n=14; Age Grp-B (9 to 12 months), n=14; and Age Grp-C (24 months), n=14. Brain oxygen tension (PBrO2), laser Doppler flow, and mean arterial pressure were measured. Final hemoglobin averaged 6.1±0.9 g/dL. PBrO2 levels decreased from a baseline of 18.1±4.1 to 17.5±6.8 mm Hg (P=0.49), and laser Doppler flow increased by 18±20% (P<0.0001) after hemodilution. Employing repeated measures multiple regression, Age Grp (P=0.30) was not a significant controlling covariate of PBrO2 in response to isovolemic hemodilution. PBrO2 levels were actually higher in Age Grp-C animals at all time points of the hemodilution protocol, although this was not statistically significant. Aged animals were also fully capable of mounting a robust local cerebral hyperemic response to the anemic challenge that was not separable from the response of younger animals.