The present study is to determine if intraislet insulin or somatostatin regulate pancreatic polypeptide (PP) secretion in the isolated perfused rat pancreas by infusing insulin or somatostatin antisera. Isolated rat panereata were stimulated with either 16.7 mMglucose (G) alone, G with antisomatostatin antibody (G + SA), or G with antiinsulin antibody (G + IA). G inhibited PP secretion −22 ± 9.5 pMbelow basal, a decrease of 9 ± 6.3% (n= 6;p= NS), G + IA inhibited PP secretion −10 ± 27.2 pMbelow basal, a decrease of 20 ± 15% (n= 7,p= NS), and G + SA stimulated PP secretion 18 ± 7.1 pMabove basal, an increase of 26 ± 5% (n= 6;p< 0.05). G stimulated insulin secretion 3,144 ± 210 pMabove basal (n= 6,p<0.05), and G + SA stimulated insulin secretion 2,695 ± 195 pMabove basal (n= 7;p< 0.05 vs. baseline,p= NS vs. G alone). G stimulated C-peptide secretion 886 ± 175 pMabove basal (n= 6;p< 0.05), G + SA stimulated C-peptide secretion 847 ± 102 pMabove basal (n= 7;p< 0.05,p= NS vs. G alone), and G + IA stimulated C-peptide secretion 834 ± 93 pMabove basal (n= 7;p< 0.05,p= NS vs. G alone). These data demonstrate that infusion of SA results in significant stimulation of PP secretion during high-G infusion, whereas IA has no effect. Infusions of SA or IA at the doses used have no effect on G-stimulated insulin or C-peptide secretion. This suggests that intraislet somatostatin may be an inhibitory regulator of PF secretion in the isolated perfused rat pancreas.