Transient ischemia produced marked memory dysfunctions in mice on three different tasks, spontaneous alternation, elevated plus-maze and passive avoidance, as tested 1, 1–2, and 2–3 days after ischemic insult, respectively. U-50,488H, a κ-opioid receptor, agonist, administered 20 min before ischemic insult markedly prevented the impairment of spontaneous alternation, the prolongation of transfer latency in elevated-plus maze and the shortening of step-through latency in passive avoidance induced by transient ischemia. The protective effect of U-50,488H (30 mg/kg) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 μg, i.c.v.), a κ-selective opioid antagonist. Although U-50,488H (30 mg/kg) did not affect body temperature in sham mice, it blocked hypothermia induced by ischemic insult. These results suggest that the protective effect of U-50,488H on memory dysfunctions in the ischemic mice is associated with the activation of κ-opioid receptors and is not based upon hypothermia.