The effects of L-364,718, a cholecystokinin receptor antagonist, on cholecystokinin octapeptide-induced inhibition of food, and its effect on food intake when given alone, were studied in mice using several different feeding paradigms. In all studies, L-364,718 (100 micrograms/kg, 1.0 mg/kg) reversed the ability of cholecystokinin octapeptide to decrease food intake. L-364,718 enhanced food consumption compared with controls in nonfasted mice (100 microgram/kg) and in prefed mice (50, 100, 250 micrograms/kg). The number of reinforcements, using a lever press, was also enhanced by L-364,718 (100 micrograms/kg) compared with control. In other paradigms, L-364,718 failed to enhance food intake. These results are compatible with the suggestion that cholecystokinin may play a physiological role in the regulation of food intake.