To investigate the insulinotropic effect of gastric inhibitory polypeptide (GIP) in chronic pancreatitis (CP), We examined the GIP response to 75 g oral glucose in 18 CP patients and 7 normal subjects (controls) by a radioimmunoassay for human GIP. The GIP response of CP patients was correlated with the pancreatic exocrine function which was evaluated by the caerulein-secretin test (CS test). Plasma GIP concentrations following the oral administration of glucose were higher in CP patients than in controls, but the difference was not significant.When CP patients were divided into3 groups according to their exocrine dysfunction (mild, moderate and severe), plasma GIP levels of CP patients with severe exocrine dysfunctionwere significantly higher than those of controls. No correlation was found between the volume and mean bicarbonate concentration and plasma GIP level at 30 min after the glucose ingestion. Only the amylase output showed a negative correlation with plasma GIP level. A. linear positive correlation was found between the integrated insulin and integrated GIP responses to oral glucose in CP patients with severe exocrine dysfunction, whereas little correlation was observed in those with milder exocrine dysfunction. These data suggest that in CP patients, endogenous GIP augments the insulin response to oral glucose when pancreatic exocrine insufficiency progresses.