The effects of the octapeptide cholecystokinin (CCK) on hamster locomotor activity were investigated in three experiments. In Experiment 1, the effect of CCK (25, 50, 75 micrograms/kg) on morphine (2.5 mg/kg)-elicited hyperactivity was studied. Results indicated that CCK antagonized morphine-elicited hyperactivity and that CCK alone elicited hypoactivity. There were no effects of dose of CCK. In Experiment 2, the effects of intraperitoneal (IP) and subcutaneous (SC) routes of administration of CCK (25 micrograms/kg) on locomotor activity were studied. Compared to saline controls, CCK induced hypoactivity that was of greater magnitude and of longer duration when administered IP than SC. Experiment 3 was designed to replicate the route of administration effect observed in Experiment 2 and to determine whether sensitization to CCK-induced hypoactivity develops over the course of a few injections. Results indicated that CCK-induced hypoactivity was greater after IP than SC administration but that sensitization was not detectable. It is concluded that CCK antagonizes morphine-elicited hyperactivity in the hamster by acting, in part, independently of morphine to produce opposite behavioral effects.