Galanin, a 29-amino acid peptide, has been demonstrated in pancreatic nerve endings and found to inhibit insulin release in the rat. However, the data available concerning its effects on exocrine pancreatic secretion are contradictory. The aim of the present study was to evaluate the effects of a synthetic porcine galanin sequence, Gal(1-16), on stimulated pancreatic secretion in hyperglycemic anesthetized and conscious rats. Male Wistar rats were anesthetized and surgically prepared with pancreatic and femoral vein catheters. In anesthetized animals, the pancreatic secretion was continuously stimulated with 150 ng cholecystokinin octapeptide (CCK-8)/kg body weight per 30 min, dissolved in saline or 10% glucose. Synthetic Gal(1-16) (0.3 or 1 nmol/kg per h) was infused over a 60-min period. In conscious rats, 1, 3, or 10 nmol Gal(1-16)/kg per h was administered in a continuous saline or 10% glucose infusion over a 30-min period. The pancreatic secretory volume and protein output were determined in 30-min samples in both models. In anesthetized rats, 0.3 nmol Gal(1-16)/kg per h did not modify pancreatic secretion during CCK-8 stimulation. However, both the pancreatic secretory volume and the protein output were significantly inhibited compared with the basal levels by 1 nmol Gal(1-16)/kg per h. The inhibitory effect of Gal(1-16) on pancreatic secretion was more marked with CCK-8/glucose (53.9%) than with CCK-8/saline stimulation (20.1%). In conscious rats, significant inhibitory effects of 1 nmol Gal(1-16)/kg per h in saline were observed (18%). During glucose infusion, a dose-dependent inhibition of 1, 3, and 10 nmol Gal(1-16)/kg per h on pancreatic secretory volume and protein output (35% inhibition at 1 nmol/kg per h) was observed. In conclusion, the inhibitory effect of Gal(1-16) on exogenous and endogenous CCK-stimulated pancreatic secretion was found to be more potent in the presence of glucose both in anesthetized and in conscious rats. These results may suggest an indirect (insulin-mediated) inhibitory effect of porcine Gal(1-16) on pancreatic secretion in the rat.