Although exogenous administration of the peptide cholecystokinin (CCK) has been shown to reduce food intake in a variety of experimental situations, few studies have examined the influence of dietary content upon CCK's effectiveness, particularly in obese states. To evaluate the effectiveness of CCK administration in animals consuming high fat diets, groups of obese and lean Zucker rats were amintained on laboratory chow (CH), a high fat diet isocaloric to chow (IF), or a hypercaloric fat diet (HF). After a 17 hr fast, rats were given intraperitoneal injections of saline or ascending doses of 0.06 to 2.0 μg/kg of the synthetic octapeptide of CCK. On all diets, obese rats required higher doses of CCK to significantly reduce feeding and showed smaller intake reductions than lean rats (p<0.001). Despite higher baseline caloric intakes (p<0.001), rats of both genotypes maintained on HF displayed larger reductions of intake than those fed IF or CH (p<0.001). Intake reductions by either genotype maintained on IF or CH were not reliably different. The manner in which the satiety effect of CCK was enhanced in rats consuming the calorically dense, palatable HF diet is unclear but may be related to orosensory and/or postingestive attributes of the diet.