In pancreatic acinar cells several neurotransmitters or hormones like acetylcholine (ACh) or cholecystokinin (CCK) lead to IP₃triggered intracellular Ca²⁺ release. Subsequently the empty stores activate "store-operated Ca²⁺ influx" (SOC). Ca²⁺ from both sources is necessary for secretion of digestive enzymes. Here we describe that SOC is stronger activated by CCK than by ACh. The reason for the smaller Ca²⁺-entry in case of ACh activation is a down regulation (max. 80 %) of SOC by ACh. Other secretagogues did not show this effect nore was it present in cell types like BHK or CHO which do not posses muscarinic receptors. Transfection and expression of DNA for muscarinic receptor-subtypes 1 and 3 in those cells fully constituted the ACh induced inhibition of Ca²⁺ entry. The reduced SOC after ACh stimulation should also reduce the secretion rat of pancreatic acinar cells. Indeed measurements of amylase secretion revealed that the maximal secretion rate after CCK stimulation was higher (400 % of control) than after ACh stimulation (250%). Moreover costimulation of cells with CCK and ACh reduced the secretion rate to a level which was typical for ACh alone. We conclude that a muscarinic block of SOC exists in pancreatic acinar cells. This block may help to integrate simultaneous signals on the level of the cytoplasmic Ca²⁺ concentration in a way that the ACh signal is preferencial in long lasting secretion processes.