Pancreatic acinar cells possess both high low affinity receptors for cholecystokinin. The cholecystokinin analog caerulein, which exerts a trophic effect on the rat pancreas, acts as an agonist at both types of receptors. In contrast, the synthetic analog CCK-JMV-180, which also acts as an agonist at high affinity receptors, opposes the action of caerulein on the low affinity receptors. We report that infusion of either caerulein or CCK-JMV-180 into rats increases [3H]-thymidine incorporation into pancreatic DNA and causes the pancreatic weight as well as content of DNA, RNA, and protein to increase. CCK-JMV-180 also stimulates in-vitro incorporation of [3H]-thymidine into DNA of cultured rat acini. The finding that both caerulein and CCK-JMV-180 exert the same trophic effect on pancreatic acinar cells indicates that this effect is mediated via high affinity acinar cell cholecystokinin receptors.