The aim of this study was to examine the effect of total parenteral nutrition (TPN) on the endocrine and exocine function of the pancreas. Endocrine function was investigated using an intravenous glucose tolerance test (IGTT) in rats with TPN for 7 or 14 days. Exocrine function was evaluated by measuring amylase secretion from isolated acini as well as pancreatic weight, water content, protein, and enzymes after 7 days of TPN. When the TPN rats were compared with the controls, the glucose tolerance curve after an IGTT was unchanged, the basal plasma insulin levels were slightly lower and the insulin secretory response to intravenous glucose was markedly impaired. No differences could be seen between the insulin response after 7 days and that after 14 days of TPN. The weight of pancreas, the total content and concentration of pancreatic protein, and the total amylase content of the pancreas were lower, whereas the total content of both chymotrypsin and trypsin was higher. The concentration of DNA remained intact, whereas the total DNA content decreased. The levels of lipolytic enzymes, except for carboxylesterlipase, were unaffected. After TPN treatment, the insulin secretory response to glucose is impaired, the exocrine pancreas is hypoplastic and the storage pattern of pancreatic exocrine enzymes is altered.