Enterostatin (APGPR) found in the gastrointestinal tract and brain is an anorectic pentapeptide. We found that APGPR inhibited morphine-induced analgesia after intracerebroventricular administration in mice at a dose of 10nmol/mouse. The anti-analgesic effect of APGPR was inhibited by pretreatment with lorglumide and LY225910, antagonists for cholecystokinin 1 (CCK 1 ) and cholecystokinin 2 (CCK 2 ) receptors, respectively. The anti-analgesic effect of APGPR may be mediated by CCK release, since APGPR does not have affinity for CCK receptors.