The effect of a prolonged 5-day fast on the blood concentrations of vasoactive intestinal polypeptide (VIP), secretin, human pancreatic polypeptide (hPP), gastrin, and group I pepsinogens (PG I) was studied in 11 healthy subjects. During the fast there was a marked increase in the concentrations of VIP, secretin, and hPP, whereas the rise in the concentrations of gastrin and PG I was less pronounced. Refeeding suppressed the increased concentration of VIP and caused elevated postprandial concentrations of secretin and hPP, whereas starvation did not influence the postprandial release of gastrin and PG I. The study shows that prolonged starvation has a pronounced effect on gut endocrine responses.