Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release.