BACKGROUND The high lipid solubility that permits rapid transfer across the blood-brain barrier makes propofol attractive for intracarotid injection. The authors hypothesized that intracarotid injection produces electrocerebral silence at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects. METHODS The authors compared the systemic and cerebrovascular effects of intracarotid and intravenous propofol during transient (10 s) and sustained (1 h) electrocerebral silence in anesthetized New Zealand White rabbits. Hemispheric electrocerebral activity, mean arterial blood pressure, ipsilateral and contralateral cerebral blood flow, tympanic temperature, and end-tidal carbon dioxide were continuously monitored in these animals. Changes in outcome variables were analyzed at four time points: at baseline, during electrical silence, during burst suppression, and after recovery of electrocerebral activity. Propofol (1%) was injected as intracarotid (0.1 ml) or intravenous (0.5 ml) boluses. RESULTS Intracarotid propofol produced electrocerebral silence at one fifth (sustained silence) to one tenth (transient silence) of the intravenous dose. Compared with baseline values, the mean arterial pressure and ipsilateral cerebral blood flow remained unchanged or decreased transiently during electrocerebral silence with intracarotid propofol. In contrast, intravenous propofol resulted in systemic hypotension and a decrease in ipsilateral cerebral blood flow. CONCLUSIONS Intracarotid propofol resulted in electrocerebral silence at a fraction of the intravenous dose that was not associated with systemic hypotension or a sustained decrease in the cerebral blood flow. Intracarotid propofol could be potentially useful for providing electrocerebral silence when cerebral perfusion is at risk.