Morphine (10 mg/kg, SC) in combination with ICV vehicle induced a significant hyperthermic effect at 120 min (peak time) after injection compared to ICV vehicle plus SC saline (control group). Glibenclamide (50 micrograms, ICV), a selective adenosine triphosphate-sensitive potassium (KATP) channel blocker, in combination with SC saline hardly affected the rectal temperature compared to the control group. ICV glibenclamide antagonized the hyperthermia induced by SC morphine in a dose-dependent manner. From these results, we demonstrated that KATP channels play an important role as modulators of the hyperthermic effect of mu agonists.