The effects of cholecystokinin (CCK) on pancreatic ornithine decarboxylase (ODC) gene expression were studied in the rat. Plasma CCK concentrations were raised to levels comparable to postprandial values either by intravenous infusion of CCK octapeptide (CCK-8) or by intraduodenal perfusion of soybean trypsin inhibitor (SBTI). ODC mRNA levels were quantified using a cloned cDNA probe. ODC mRNA increased to 166 ± 34% (n = 4) of control after 1 h, peaked at 254 ± 39% (n = 4) of control after 24 h, and remained significantly elevated for up to 48 h of SBTI infusion. Intravenous infusion of CCK-8 for 24 h increased ODC mRNA levels of the same extent observed with SBTI infusion. The CCK receptor antagonist L364,718 by itself had no effect on ODC mRNA by both intravenous CCK infusion and intraduodenal infusion of SBTI. These data therefore indicate that CCK plasma concentrations comparable to postprandial values regulate pancreatic ODC at a pretranslational level and that SBTI exerts its effects on pancreatic ODC via an increase in plasma CCK.