The author reviews the findings obtained with CCK antagonists in several experimental models of pancreatitis and highlights the harmful effects of L364,718-a potent CCK-receptor antagonist-on acute pancreatitis (AP) induced by bilepancreatic duct obstruction (BPDO) recently reported by De Dios et al. (2). Although the title of the paper may be appropriated for attracting the attention of readers it is highly confusing, since although L364,718 was shown to increase cytosolic calcium levels in acinar cells of control rats, no evidence of AP was found by De Dios et al. (2). In fact, it is well documented that while an increase in intracellular Ca 2+ concentration is required for the activation of trypsinogen in acinar cells exposed to supramaximal dosis of CCK (3-5), it was not sufficient, by itself, to initiate enzyme activation in the absence of the secretagogue (5). In contrast, L364,718 increased the severity of AP in rats subjected to BPDO (2), because apart from increasing citosolic calcium, it was not able to prevent the accumulation of enzymes in acinar cells at early stages of AP, when trypsinogen is highly activated in the presence of Ca 2+ .A common feature in the clinical setting and any experimental model of AP is the blockade of acinar secretion. As a result, the feedback mechanism for CCK release from duodenal mucosa is inhibited and CCK plasma levels are thereby increased. On this basis, it is thought that CCK could play an important role in the development of AP, and thereby different treatments with CCK antagonists have been extensively applied in AP models with different results. As expected a priori, CCK antagonists have been shown to decrease the severity of AP induced by supramaximal dosis of CCK or its analogue cerulein (6-10). Beneficial effects have been reported by Niedereau et al. on AP induced CDE diet (11) and BPDO (12), but CCK antagonists failed to show protective effects on AP induced by L-arginine (13), CDE diet in mice (14, 15), and BPDO (16). Niedereau (1) questions the detrimental effects of L364,718 in AP-induced by BPDO shown by De Dios et al.(2) based on the fact that the hyperamylasemia observed in BPDO rats treated with L364,718 was lower than in nontreated BPDO rats. Nevertheless, it is noteworthy that no statistically significant difference was found between either animal group. According to these observations, we could have concluded that no beneficial effect is exerted by the CCK antagonist on AP development. However, different data support the notion that L364,718 exacerbates AP induced by BPDO, such as the significantly higher values of hematocrit and ascites volume, the more severe lesions observed in blinded pancreatic sections by electron microscopy (2), and the results reported by Uruñuela et al. (17) on pancreatic fluid content (edema), plasma TNF-α levels, glutathione depletion, and oxygen free radicals within acinar cells, all of whose values were significantly higher in L364,178-treated than in nontreated BPDO rats. There is evidence to indicate that L364,718 in...