The ontogenesis of pancreatic thyrotropin-releasing hormone (TRH) in the human fetal gland was studied by radioimmunoassay or immunocytochemistry. The highest TRH concentrations (1,508.5 +/- 382.3 pg/mg wet wt) were detected between 6 and 8 wk of gestation. From 9 to 12 wk, TRH declined to 365.2 +/- 127.4 pg/mg wet wt and remained low thereafter (96.1 +/- 28.9 pg/mg wet wt). The immunocytochemical procedure was performed on semithin and thin sections from 12- to 19-wk-old human fetuses. At the light microscope level, TRH was found interspersed among the islet cell clusters (12 wk), and later (16 wk) inside the typical islets of Langerhans. Consecutive semithin sections treated by TRH and insulin antisera showed the same immunoreactive cells. Electron microscopy showed TRH in B cell secretory granules. These results are consistent with an eventual implication of TRH in the endocrine regulation of metabolism or in the fetal development of pancreas.