Hypothermia has a neuroprotective effect for ischemia. The aim of this study was, therefore, to determine whether mild hypothermia (35°C) would enhance neuroprotecive effects of immunosuppressant FK 506 for focal ischemia. The left MCAO were occluded for 2 h by intraluminal suture and reperfused for 24 h. Animals were randomly devided into the following four groups. (I) vehicle-treated, normothermic (37°C) group (II) vehicle-treated, mild hypothermic (35°C) group (III) FK 506-treated, normothermic (37°C) group (IV) FK 506-treated, mild hypothermic (35°C) group. FK 506-treated animals received a single injection of FK 506 (0.3 mg/kg) intravenously 120 min after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. The cortical and striatal infarct volume in group IV was significantly reduced compared with that in group I (p<0.001), whereas there was no significant difference between group II or III and group I. Moreover, edema volume in group IV was significantly smaller than that in group I (p<0.05). These results demonstrate that a combined therapy with mild hypothermia (35°C) and FK 506, each has no neuroprotective effects alone, significantly reduces the ischemic brain damage and enhances neuroprotecive actions for focal ischemia in rats.