The aim of this study is to investigate the effects of ghrelin and GH-releasing peptide-6 (GHRP-6) on the release of growth hormone (GH), adrenocorticotrophic hormone (ACTH), and cortisol in dogs with pituitary-dependent hyperadrenocorticism (PDH) and in healthy dogs of comparable age. In eight healthy dogs, the responses to ghrelin and GHRP-6 were compared to those of GH-releasing hormone (GHRH) and NaCl 0.9% (control). In seven dogs with PDH, the effects of ghrelin and GHRP-6 were compared with their effects in healthy dogs. In the healthy dogs, GHRH, GHRP-6, and ghrelin caused a significant rise in plasma GH concentrations. GHRH administration elicited significantly higher plasma GH concentrations than administration of ghrelin and GHRP-6. In the dogs with PDH, the GHRP-6-induced release of GH was significantly lower than in healthy dogs. Administration of ghrelin elicited a GH release that did not differ significantly between dogs with PDH and healthy dogs. Ghrelin and GHRP-6 did not cause a significant rise in plasma ACTH and cortisol concentrations in either the healthy dogs or the dogs with PDH. It is concluded that in comparison with GHRH, GHRP-6 and ghrelin have a low GH-releasing potency in healthy dogs. In dogs with PDH, the GH release in response to GHRP-6 is impaired. Neither GHRP-6 nor ghrelin activates the pituitary-adrenocortical axis in healthy elderly dogs and dogs with PDH.