The effects of cholecystokinin (CCK) on [3H]leucine incorporation into protein were studied in isolated pancreatic acini from normal and streptozotocin-induced diabetic rats. CCK8, the biologically active C-terminal octapeptide of CCK, increased [3H]leucine incorporation into protein over a concentration range that stimulates digestive enzyme secretion (1 X 10(-11) to 1 X 10(-10) M); at higher concentrations, CCK8 inhibited incorporation. Stimulation of [3H]leucine incorporation was greatest in acini from diabetic rats, intermediate in acini from fed normal rats, and least in acini from fasted rats. The magnitude of inhibition was similar in all acini. A significant stimulatory effect of CCK8 in acini from diabetic rats was detected after 10 min and was maximal after 40 min of incubation. Carbachol mimicked both the stimulatory and inhibitory effects of CCK, whereas the Ca2+ ionophore A23187 mimicked only the inhibitory effects. Insulin also stimulated [3H]leucine incorporation in acini from diabetic rats, and its effects were additive to the stimulatory effect of CCK. The present findings suggest that physiological concentrations of CCK and other pancreatic secretagogues may participate in the regulation of pancreatic protein synthesis.