Rats were implanted in the striatum with a Pt/Ir electrode for measurement of regional cerebral blood flow (rCBF) (H2 clearance technique), a carbon paste electrode for monitoring tissue oxygen and a glucose biosensor for monitoring extracellular glucose. Changes in all three parameters were recorded in response to the intraperitoneal (i.p.) administration of the anesthetics chloral hydrate (350 mg/kg), sodium pentobarbitone (60 mg/kg) and ketamine (200 mg/kg). An i.p. injection of normal saline, given as a control for the injection of the anesthetics, produced a parallel increase in rCBF and tissue oxygen accompanied by a brief decrease in extracellular glucose. Changes in tissue oxygen reflected the changes in rCBF; there was a decrease in both after sodium pentobarbitone, a decrease followed by a rebound after ketamine and a transient increase after chloral hydrate. All three anesthetics produced a decrease in extracellular glucose. The disparity between the changes in glucose and the changes in rCBF and oxygen suggests that during anesthesia, the reduction in extracellular glucose is not due to a reduction in the direct delivery of glucose from the blood vascular system. These results also indicate that levels of enzymatic substrates and mediators, which are intrinsic to the design and operation of amperometric biosensors, are clearly altered in a complex manner by anesthesia and suggest that caution should be exercised in extrapolating data from acute anesthetized experiments to normal physiology.