Background-Recent studies indicate that gastric emptying may be influenced by patterns of previous nutrient intake. Endogenous cholecystokinin (CCK), whose synthesis and release can be aVected by dietary intake, has a major role in the regulation of gastric emptying. Aims-To evaluate the influence of diets with diVering protein content on gastric emptying of diVering liquid test meals and plasma CCK levels in the rat and to check whether the inhibitory eVect of exogenous CCK on gastric emptying is modified after long term intake of diets with diVering protein content. Methods-Rats were fed for three weeks with high protein, medium protein (regular), or low protein diet. On day 22 gastric emptying of a peptone meal was studied. In addition, basal and postprandial CCK levels after the diVerent dietary regimens were measured by bioassay. The time course of dietary adaptation was studied and its specificity assessed through the use of diVerent (peptone, glucose, and methylcellulose) test meals. The eVect of exogenous CCK-8 on gastric emptying was studied at the end of the adaptation period (three weeks). Results-Feeding the animals with a high protein diet for three weeks resulted in a significant (p<0.05) acceleration (by 21.2 (8.2)%) of gastric emptying while feeding with a low protein diet was followed by a significant (p<0.05) delay (by 24.0 (6.2)%) in the emptying rate. When the time course of the eVect of dietary adaptation on gastric emptying was studied, it appeared that at least two weeks are required for dietary protein to be eVective. The regulatory eVect of dietary protein on gastric emptying proved to be dependent on meal composition. Only the emptying rate of a protein containing meal (40% peptone) was significantly modified by previous dietary intake. No significant (p>0.05) changes were observed with glucose and methylcellulose meals whose emptying rates were similar in rats receiving a high protein or low protein diet. A peptone meal strongly and significantly (p<0.05) increased plasma CCK levels in rats fed a medium protein (regular) diet. Results were similar in rats receiving a low protein diet (p<0.05) but not in rats on a high protein diet (p>0.05). As a consequence, postprandial plasma levels of CCK in rats fed with a medium or low protein diet were significantly (p<0.05) higher than those in rats receiving a high protein diet. In rats on high and low protein diets, dose response curves to CCK-8 were virtually identical, suggesting that dietary protein intake has no influence on the eVect of exogenous CCK. Conclusions-These results clearly show that gastric emptying of a protein containing meal can be modified by previous dietary protein intake. This eVect, which is time dependent and meal specific, may be related to changes in endogenous CCK release which will aVect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, these results emphasise the importance of dietary history in the evaluation and interpretation of gastri...