Introduction: Validity of determination of transcranial doppler flow velocity in the middle cerebral artery as a measure for cerebral blood flow is discussed controversely. We have investigated the correlation between transcranial doppler flow velocity in the middle cerebral artery and the regional cerebral blood flow measured with the radioactive microspheres method in pigs. Materials and methods: The animals were randomly divided into xenon group (n=5), which received anaesthesia with 70% xenon inhaled in 30% oxygen in addition to buprenorphine 15 μgkg^-1h^-1. The TIVA group (n=5) was anaesthetized with a continuous infusion of pentobarbital at a rate of 15 mgkg^-1h^-1 and buprenorphine at a rate of 15 μgkg^-1h^-1. Under normoventilation heart rate, mean arterial pressure, arterial oxygen saturation, arterial pH, arterial pCO₂ and temperature were determined. Then hyper- and hypoventilation was carded out and controlled by measuring expiratory CO₂ levels and arterial blood gases. Transcranial doppler flow velocity was measured in normo-(target p(a)CO₂-40 mmHg), hyper- (target p(a)CO₂=30mmHg) and hypoventilation (target p(a)CO₂=50mmHg). Simultaneously radiolabelled microspheres with three different radioactive markers (Niobium 95, Rutenium 103, Cereum 141) were injected into the left ventricle. Three tissue aliquots were taken from several parts of the brain (cortex, brainstem, medulla oblongata and cerbellum) to calculate the regional cerebral flow by measuring radioactivity. A total number of 252 microsphere samples were studied. Results: We found a good correlation between transcranial doppler flow velocity and cerebral blood flow measured with the microspheres method in pigs. The regional changes of CBF in cortex, brainstem, medulla and cerebellum were parallel, revealing a nearly equal change on cerebral blood flow in the different regions of the brain due to ventilatory manipulations under xenon or total intravenous anaesthesia. Discussion: We conclude, that the transcranial doppler flow velocity measurement in the middle cerebral artery is a reliable and useful non-invasive method to estimate cerebral blood flow.