In the brain hyperammonemia interferes with ion homeostasis, membrane potentials, neurotransmission, and neurotransmitter recycling and reduces metabolic rates for oxygen and glucose. Because, cerebral blood flow (CBF) is closely coupled to metabolism, CBF is most often reduced in diseases associated with hyperammonemia. However, in severe cases of hyperammonemia, as in patients with acute liver failure, Reye's syndrome, and inherited metabolic disorders of the urea cycle, the normal regulation of CBF is also impaired. One of the most prominent findings is a failure of CBF autoregulation that uncouples metabolism from CBF. Clinically failure of autoregulation may imply that both cerebral hypoxia and hyperaemia may develop in the patient depending on the driving pressure of the brain, i.e., cerebral perfusion pressure. In addition a gradual "nonreactive" dilatation of the cerebral arterioles often aggravates the mismatch between nutritive demands and delivery in the brain. The reason for arteriolar dilation and homogeneous capillary blood flow is not settled but seems not to be mediated by excessive release of nitro oxide. More likely the arachidonic acid cascade with increased synthesis of prostaglandins, cytochrome P450 metabolites, and potassium channel activation are implicated in this vasodilatation. The combination of cerebral hyperaemia, increased hydrostatic capillary blood pressure, and accumulation of organic and nonorganic osmolytes within the brain during hyperammonemia clearly will favor cerebral capillary water influx. This imbalance between colloid osmotic and hydrostatic pressures in patients with severe hyperammonemia means that simple interventions based on physiological principles may help ameliorate cerebral hyperaemia and water influx. Thus, it is suggested that not only monitoring of intracranial pressure (ICP) and cerebral perfusion are pivotal to help prevent high ICP but also basic clinical information, such as Tp, PaCO2, and plasma sodium/glucose concentrations, should be closely followed and corrected.