Hypothalamic hormones physiologically regulate pulsatile release of growth hormone (GH) from the anterior pituitary gland. Since the discovery of these hormones in the 1970s, several new chemically synthesized peptidyl and nonpeptidyl derivatives have been proved to stimulate and amplify GH secretion, and this series of molecules has been named the growth hormone secretagogues (GHSs). One of these compounds led to the discovery of a GPCR-type receptor for GHSs (GHS-R), and subsequently the endogenous ligand for the receptor has been identified, and is referred to as ghrelin. The identification of GHSs as physiological regulators of GH secretion encouraged us to examine our GHSs pharmacologically. We previously reported that novel oxindole derivatives have been identified as GHS-R agonists from our internal chemical library. Among these derivatives, (+)-6-carbamoyl-3-(2-chlorophenyl)-(2-diethylaminoethyl)-4- trifluoromethyloxindole (SM-130686, 37S) was found to have potent activity in vitro with a good pharmacokinetic profile in rats (bioavailability of 28%). In this article, we review the synthesis and pharmacological evaluation of SM-130686. SM-130686 binds specifically to GHS-R and increases the Ca2+ concentration in Chinese hamster ovary cells expressing recombinant GHS-R. Maximal enhancement of the intracellular Ca2+ concentration induced by SM-130686 treatment was approximately 55% that induced by ghrelin, suggesting that SM-130686 may be a partial GHS-R agonist. Also, in in vivo studies, oral administration of SM-130686 increased body length and fat-free mass gain. We compare the pharmacological profile of SM-130686 with other GHSs, including GHRH and ghrelin, and discuss the therapeutic usefulness of GHSs against several disorders, as well as for treatment of GH deficiency.