Changes in cerebral high-energy phosphate stores and lactate concentration (as evidence for cerebral protection) were studied in dogs treated with etomidate during incomplete global ischemia, which was of a magnitude insufficient to abolish neuronal synaptic activity (as evidenced by electrical activity on EEG). In six dogs the effects of etomidate (5 mg X kg-1) on the rates of adenosine triphosphate (ATP) and phosphocreatine (PCr) depletion and lactate accumulation during 9 min of oligemic hypotension to 31 mmHg were compared with six untreated dogs. In the dogs treated with etomidate the cerebral energy stores of ATP and PCr and the cerebral energy charge were maintained at higher levels than in the untreated dogs, and the cerebral lactate accumulation was significantly less. This effect of etomidate is similar to that of other anesthetics (thiopental and isoflurane) in this model. The authors conclude that in circumstances of ischemia that are insufficient to abolish neuronal synaptic activity, etomidate may improve tolerance of the brain to ischemia by decreasing cerebral metabolism through its suppression of neuronal synaptic activity.