Our aim was to determine if mucosal mast cells could be activated by endogenous CCK and, as a consequence, mediate CCK actions in the small intestine. Rats were prepared for electromyography to record electrical activity in the small intestine. In another group of animals, the duodenum was perfused to measure rat mast cell protease II (RMCP II) as indicative of mast cell degranulation. Endogenous CCK release was induced by administration of soybean trypsin inhibitor (SBTI) in conscious rats or by intraduodenal perfusion of ovalbumin hydrolysate (OVH) in anesthetized rats. CCK concentration was measured by bioassay on pancreatic acini. SBTI in control rats disrupted migrating motor complexes (MMC) for >40 min. In rats treated with the mast cell stabilizer ketotifen, SBTI did not induce any change in the MMC pattern. RMCP II concentration in the duodenal perfusate significantly increased after OVH. Perfusate from ketotifen-treated animals did not show any significant increase in RMCP II values during OVH perfusion, although CCK plasma concentration was not different from the control group. Furthermore, infusion of the CCK-B receptor antagonist L-365,260 significantly blocked the increase of RMCP II concentration after OVH. Our results indicate that mucosal mast cells are degranulated by endogenous CCK release through stimulation of CCK-B receptors. Therefore mucosal mast cells participate in CCK intestinal actions.