Rats maintained on low-fat (LF) or high-fat (HF) diets were fitted with gastric cannulas and duodenal catheters. Intraperitoneal injection of 0.250-2.0 microg/kg cholecystokinin (CCK) significantly inhibited gastric emptying of a 5-ml NaCl load in LF rats by 26.2-55. 1% compared with emptying after vehicle injection. By contrast, CCK-induced inhibition of gastric emptying was significantly less in HF rats given the same CCK doses (10.0-31.7% inhibition over the same CCK dose range). A 20-min intraduodenal infusion of oleate (0.03 or 0.06 kcal/ml) also resulted in significant inhibition of gastric emptying in LF rats (24 and 89%, respectively). Oleate-induced inhibition of gastric emptying was significantly attenuated in rats maintained on the HF diet (2 and 56%, respectively). Unlike CCK injections or oleate infusion, intraduodenal maltotriose infusion inhibited gastric emptying to a similar degree in LF and HF rats (77 and 78%, respectively). These results indicate that feeding HF diets diminishes the enterogastric inhibition of gastric emptying by intestinal oleate and diminishes the ability of CCK to inhibit gastric emptying.