Background: There is evidence from studies in animals that the effects of both fat and cholecystokinin (CCK) on gastrointestinal function and energy intake are attenuated by consumption of a high-fat diet. Hypothesis: In humans, the effects of exogenous CCK-8 on antropyloroduodenal motility, plasma CCK, PYY and ghrelin concentrations, appetite and energy intake are attenuated by a high-fat diet. Design: 10 healthy lean males consumed isocaloric diets (~15,400 kJ per day), containing either 44 % (high-fat; 'HF') or 9 % (low-fat; 'LF') fat, for 21 days in single-blind, randomized, cross-over fashion. Immediately following each diet (i.e. on day 22), subjects received a 45-min intravenous infusion of CCK-8 (2 ng/kg/min), and effects on antropyloroduodenal motility, plasma CCK, PYY and ghrelin concentrations, hunger and fullness were determined. 30 min after commencement of the infusion, subjects were offered a buffet-style meal, from which energy intake (kJ) was quantified. Results: Body weight was unaffected by the diets. Fasting CCK (P<0.05), but not PYY and ghrelin, concentrations were greater following the HF, compared with the LF, diet. Infusion of CCK-8 stimulated pyloric pressures (P<0.01) and suppressed antral and duodenal pressures (P<0.05), with no difference between the diets. Energy intake also did not differ between the diets. Conclusions: Short-term consumption of a HF diet increases fasting plasma CCK concentrations, but does not affect upper gut motility, PYY and ghrelin, or energy intake during CCK-8 infusion, in a dose of 2 ng/kg/min, in healthy males.