Histidyl-proline diketopiperazine (His-Pro DKP) cells in the pancreas of human fetuses aged between 12 and 19 wk were localized by the indirect antibody-enzyme method on semithin sections. To study their fine structure, two techniques were used: a superimposition technique consisting of comparison of the same cells in semithin and electron microscopic preparations, and an immunocytochemical technique on ultrathin sections using the unlabeled antibody peroxidase-antiperoxidase method. Our results show that (a) the same cells are positive for both His-Pro DKP and glucagon/glicentin, (b) His-Pro DKP immunoreactive cells possess extremely electron-opaque secretory granules, implying that these cells correspond to the A cells, and (c) HisPro DKP immunoreactivity is found over the secretory granules. We hypothesize that the two peptides His-Pro DKP and thyrotropin-releasing hormone (TRH) have independent origins, since TRH is found in the B cells.