Alterations in blood CO] tension (paco) are frequently used in neurosurgical Intensive Care Units to manage patients with severe brain diseases and to test the status of mechanisms regulating cerebral blood flow. In this work, the complex relationships between Pacc>2> cerebral blood volume, cerebral blood flow and intracranial pressure (ICP) are investigated by means of an original mathematical model. The model incorporates the intracranial compliance, the cerebrospinal fluid production and reabsorption processes, the collapse of the terminal cerebral veins, and the active response of large and small cerebral arteries to perfusion pressure changes (autoregulation) and to changes inpaCO; (chemical regulation). Two different kinds of simulations have been performed to validate the model and to test its possible clinical usefulness. In a first stage, ICP was maintained constant to mimic experiments with the open skull and the ccrebrovascular response to changes in systemic arterial pressure and in Paco^ was reproduced. The results of the model show that agreement with the experimental curves of various authors is quite good. In the second stage, conditions occurring with a closed skull were simulated. These are characterized by acute changes in ICP, induced by active changes in cerebral blood volume. In these conditions, the model was used to reproduce the time pattern of ICP and blood flow velocity at the level of the middle cerebral artery observed in patients during alterations in systemic arterial pressure and Paco^A comparison between simulation results and real tracings is presented and discussed. The model may represent a valid tool to interpret the complex relationships between cerebral hemodynamic quantities in neurosurgical Intensive Care Units. Transactions on Biomedicine and Health vol 4, © 1997 WIT Press, www.witpress.com, ISSN 1743-3525