The effect of endogenous hyperinsulinaemia, produced by syngeneic transplantation of rat insulinoma at an extrapancreatic site, on pancreatic insulin and pancreatic polypeptide has been examined by radioimmunoassay and immunohistochemistry. Twenty days after subcutaneous transplantation, tumour-bearing rats exhibited marked hyperinsulinaemia and hypoglycaemia, with plasma pancreatic polypeptide concentrations similar to controls. Immunoreactive insulin levels in the head and tail of pancreas of tumour-bearing rats were reduced by 90–95% compared with control animals. Immunoreactive pancreatic polypeptide levels in the head of the pancreas were reduced by 70%, but the relatively low levels of peptide in the pancreatic tail were similar in tumour-bearing and control rats. Insulin and pancreatic polypeptide cells were weakly immunofluorescent in tumour-bearing rat pancreas. In conclusion, the presence of an insulinoma at an extrapancreatic site resulted in a severe depletion of endogenous insulin and pancreatic polypeptide, suggesting that there is a functional relationship between the beta and pancreatic polypeptide cell.