Thyrotropin-releasing hormone (TRH) stimulated in vivo growth hormone (GH) release in conscious and anesthetized young domestic fowl. The administration of the presumed metabolites of TRH, deamido-TRH (TRH-OH) and histidyl-proline diketopiperazine (HPD), was followed by small but significant (p < 0.05) increases in the plasma concentrations of GH in both conscious and anesthetized chicks. However, the ability of TRH-OH or HPD to stimulate GH secretion was less than that observed with a 100-fold lower dose of TRH. The administration of either TRH-OH or HPD with TRH increased the GH response over that observed with TRH alone. The ability of chicken plasma to degrade exogenous TRH in vitro was determined by measuring immunoreactive TRH (IR-TRH) content and by assessing the ability of the incubated samples to increase the plasma concentration of GH when administered to young fowl. The in vitro half-life of TRH was estimated to be 9.8 (by immunoassay) and 9.6 (by a biological index) min for plasma from adult male chickens and 23.9 (by immunoassay) and 20.2 (by biological index) min for plasma from 6-week-old chicks. This difference in degradation may account, at least in part, for the observed age-related decrease in the plasma concentration of GH in birds and for the diminished GH responsiveness of adult birds to exogenous TRH.