Barbiturates are administered in a variety of clinical conditions to control elevated intracranial pressure (ICP). However, their routine use to treat elevated ICP has been questioned because it may cause severe side effects. We therefore investigated the effect of high-dose barbiturate therapy on ICP and outcome in patients with severe brain edema after severe middle cerebral artery (MCA) or hemispheric infarction. Barbiturate coma was induced with thiopental infusion in 60 patients with critically increased ICP due to large hemispheric or MCA territory infarction, defined by CT. ICP was monitored in all patients during barbiturate therapy. Barbiturate coma was induced after a standardized treatment protocol for increased ICP after failure of osmotherapy and mild hyperventilation. During barbiturate administration, cerebral perfusion pressure (CPP) and mean arterial pressure were recorded. Clinical outcome of these patients and the individual effect on ICP were analyzed. Only five of 60 patients who were treated with barbiturate coma survived (8%). All other patients died after transtentorial herniation with subsequent brain death. Barbiturate infusion was followed by a drop in ICP in 50 patients and showed no effect on ICP values in 10 patients. CPP decreased with a mean of 9 mm Hg (range, 5 to 20 mm Hg). Although barbiturates were initially effective, only in some patients was ICP control sustained. Severe side effects of barbiturate therapy, besides arterial hypotension, were seen in 15 patients (25%). Barbiturate coma in the therapy of increased ICP after severe ischemic hemispheric stroke can lower critically elevated ICP levels. However, it seems to have no positive effect on neurologic outcome.