Cerebral activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMRglc) more than it increases cerebral uptake of oxygen (CMR(O2)). To study this phenomenon, we present an application of the Kety-Schmidt technique that enables repetitive simultaneous determination of CBF, CMR(O2), CMRglc and CMRlac on awake, non-stressed animals. After constant intravenous infusion with 133Xenon, tracer infusion is terminated, and systemic arterial blood and cerebral venous blood are continuously withdrawn for 9 min. In this paper, we evaluate if the assumptions applied with the Kety-Schmidt technique are fulfilled with our application of the method. When measured twice in the same animal, the intra-individual variation for CBF, CMR(O2), and CMRglc were 10% (SD: 25%), 8% (SD: 25%), and 9% (SD: 28%), respectively. In the awake rat the values obtained for CBF, CMR(O2) and CMRglc were 106 mL [100 g](-1) min(-1), 374 micromole [100 g](-1) min(-1) and 66 micromole [100 g](-1) min(-1), respectively. The glucose taken up by the brain during wakefulness was fully accounted for by oxidation and cerebral lactate efflux. Anaesthesia with pentobarbital induced a uniform reduction of cerebral blood flow and metabolism by approximately 40%. During halothane anaesthesia CBF and CMRglc increased by approximately 50%, while CMR(O2) was unchanged.