The binding affinity of somatostatin-14 (SRIF), various SRIF derivatives, and some peptides belonging to the growth hormone-releasing peptide (GHRP) family to specific receptors for SRIF and GHRP in the human pituitary gland has been measured. GHRP receptors have been identified using [125I]Tyr-Ala-hexarelin, a peptide that thas been demonstrated to be a potent growth hormone (GH) releaser in humans. Tyr-Ala-hexarelin binding was displaced in a dose-dependent manner by different GHRPs (hexarelin, GHRP-2, and EP-51216). Surprisingly, some SRIF octapeptide derivatives such as vapreotide, lanreotide, octreotide, and their analogs were also able to displace the GHRP ligand. By contrast, no inhibition of Tyr-Ala-hexarelin binding was observed in the presence of SRIF or SRIF derivatives (SRIF H-2186, H-2485, and H-3382) that are known to have a weak SRIF-like activity. When [125I]Tyr1-SRIF-14 was used as a ligand, we observed displacement with SRIF and the octapeptide SRIF analogs but not with GHRPs and other SRIF derivatives. The results point to a sharing of the GHRP receptor with the octapeptide SRIF analogs, but not SRIF. Our data are consistent with the hypothesis that the putative natural GH secretagogue ligand may be a growth hormone release inhibiting factor that is different from SRIF and that is antagonized by GHRP.