Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canine pancreatic autograft model. To help define this inhibitory mechanism, the effect of these agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated. In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK-stimulated amylase release of pancreatic tissue slices. In vivo assessment employed animals with pancreatic autografts and pancreaticocystostomies, evaluating the effect of a bolus intravenous injection of 100 micrograms of octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with 0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylase secretion but had no significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release. These studies demonstrate that octreotide acetate has an in vivo inhibitory effect on basal amylase release of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results indicate that the exocrine inhibition produced by somatostatin analogues in the grafted pancreas occurs via an indirect mechanism.