In the chicken growth hormone (GH) secretion is predominantly controlled by two hormones, thyrotropin-releasing hormone (TRH) and somatostatin (SRIH), respectively stimulating and inhibiting GH release. In view of the hypothesis of a novel GH secretagogue (CHS) in mammals, this specific species was used to further assess the exact function of two nonpeptidyl GHSs-L-692,429 and L-163,255. Both synthetic products stimulate CH secretion directly at the level of the pituitary as shown in in vitro perifusion studies. Plasma GH levels increase within 10-15 min after a single challenge of L-692,429 or L-163,255, A SRIH pretreatment dimishes this GH response, Both CH-releasing peptide mimetics decrease hypothalamic TRH concentrations, whereas SRIH levels are not affected. The novel GHS may therefore control GH secretion both at the level of the pituitary and the hypothalamus, The present article shows that nonpeptidyl mimetics also control GH secretion in nonmammalian species suggesting that the endogenous hormone may be a conserved GH stimulator in several vertebrates. The GH response to CHS in birds may be regulated both directly at the level of the pituitary and by releasing another endogenous GH stimulator (TRH) from the hypothalamus.