In the present study, we examined the neuroprotective effect of gamma-glutamylethylamide (theanine) on the ischemic brain damage in a middle cerebral artery occlusion model in mice. Theanine was injected i.p. 3 h after the occlusion or immediately before and 3 h after the occlusion. Theanine (1 mg/kg) significantly decreased the size of the cerebral infarcts 1 day after the occlusion. In contrast, theanine did not affect the cerebral blood flow, brain temperature and physiological variables (pH, pCO(2), pO(2) and hematocrit) in this model. These results suggest that theanine directly provides neuroprotection against focal cerebral ischemia and may be clinically useful for preventing cerebral infarction.