The effects of lidocaine in high doses, i.e. higher than seizure doses, on cerebral function and metabolism are reviewed. Evidence is presented that lidocaine (160 mg/kg) reduces membrane NA+-K+ permeability, restricts leak fluxes of these ions, and decreases the load on the associated ion transport. In the ischemic brain (circulatory arrest in dogs on cardiopulmonary bypass circulation), lidocaine delays K+ efflux, indicating reduced membrane permeability. In the nonischemic brain lidocaine has two effects. One is to abolish electrocortical activity and reduce oxygen and glucose consumption accordingly ("barbiturate-like" effect). The other is a specific membrane sealing effect by which Na+-K+ leak fluxes are restricted and associated demand for active transport according reduced. By this effect lidocaine is able to reduce cerebral metabolism by an additional 15-20% below the barbiturate minimum at flat EEG. These effects of lidocaine resemble those of hypothermia and may enhance the hypothermic protection of the ischemic brain.