Neonatal rat pancreata are not responsive to stimulation by cholecystokinin (CCK) and this has been shown to be due partly to low binding of CCK to pancreatic acinar cells of rats at this age. The effect of thyroxine on the maturation of CCK receptor binding and enzyme secretion is studied. One-day-old rat pups were injected daily with thyroxine (0.1 microgram/g of body weight) for 3 days and killed on day 5. Control littermates were injected with normal saline at the same volume and schedule as the thyroxine group. The pancreatic weight and amylase activity were significantly higher in pups from the thyroxine group. Amylase release after stimulation with various concentrations of CCK was also higher in the thyroxine group. The maximal binding to [125I]BH-CCK-8 was significantly higher in dispersed acini from the thyroxine group when compared to the control group (5.2 vs. 2.0%). Analysis of binding data showed that the higher binding was due to a higher maximal binding capacity in the thyroxine group (1.1 +/- 0.41 vs. 5.2 +/- 1.4 fmol/mg of protein). Thyroxine, therefore, induces a precocious maturation of the secretory function of the pancreatic acini, specifically by modulating the maximal binding capacity of the high-affinity binding sites.