Binding of125I‐[Tyr8]‐SP to isolated pancreatic acinar cells was inhibited in a concentration‐dependent way by SP, [Tyr8]‐SP and longer C‐terminal fragments of SP. SP6–11was the shortest sequence to bind significantly to SP‐receptors as well as to stimulate amylase release from dispersed pancreatic acini. SP7–11and shorter fragments did not inhibit binding of125I‐[Tyr8]‐SP and did not stimulate secretion of amylase significantly. SP augmented the stimulatory effect of cholecystokinin on amylase release. Two SP‐antagonists, [D‐Pro2, D‐Trp7, 9]‐SP and [D‐Pro2, 4, D‐Lys3, D‐Gln5, 6, D‐Trp7, 9]‐SP inhibited binding of125I‐[Tyr8]‐SP in a concentration dependent manner and tended at a high concentration to reduce release of amylase