The effect of thyrotropin-releasing hormone (TRH) and histidyl-proline-diketopiperazine [cyclo (His-Pro), CHP] on amylase secretion from isolated rat exocrine pancreatic acinar cells was investigated. TRH showed a dose-dependent inhibition of carbachol-stimulated amylase secretion with a maximum of 24% at a concentration of 10(-11) M (p < 0.05). Basal amylase release was not affected in concentrations from 10(13) M to 10(-8) M. CHP did not influence basal or carbachol-stimulated pancreatic secretion in vitro. These results suggest that TRH in contrast to CHP may play a role in the paracrine regulation of exocrine pancreatic secretion.