Malignant cerebral infarction (MaCI) treated with mechanical ventilation, mannitol, or barbiturates has a mortality of about 80% and survivors show severe disability. When applied for 48 to 72 hours, moderate hypothermia seems to reduce the mortality rate of MaCI. However, even after 72 hours, cerebral edema is still present, and the patient's condition often worsens during rewarming. We here report, as a case series, our experience with the use of prolonged moderate hypothermia to treat patients with MaCI. Twelve MaCI patients 27 to 64 years of age were treated. All presented with middle cerebral artery occlusion and all but one with internal carotid artery occlusion. A cooling blanket was used to lower the patient's core temperature to 32 degrees C to 33 degrees C. Hypothermia was induced within 24 hours of infarction onset and was discontinued when the CT scan showed a subsiding mass effect and was followed by slow rewarming (2-5 days). Patients were mechanically ventilated while sedated with high doses of gamma-hydroxybutyrate, a naturally occurring metabolite of gamma-aminobutyric acid (GABA), which acts on the GABAB receptor. Seven patients survived for 6 months, and 6 were able to walk without assistance; the other 5 died due to early cerebral herniation (2) or progression of infarct size (3). The mean duration of hypothermia for the survivors was 19 days (range, 11-22 days). Side effects observed in all patients were systemic hypotension, thrombocytopenia, and hyperfibrinogenemia. Prolonged hypothermia with gamma-hydroxybutyrate can be used to treat MaCI patients, with a fairly good clinical outcome for survivors.