OBJECTIVE Growth hormone releasing peptides (GHRPs) are a group of synthetic compounds capable of releasing GH by an unknown mechanism. The aim of this study was to determine the effect of administering biosynthetic human growth hormone (rhGH) on the GH releasing activity of hexarelin, a new and potent GHRP, and to compare the results with those obtained with growth hormone releasing hormone (GHRH). METHODS Boluses of saline or rhGH were administered intravenously, followed 90 minutes later by a second intravenous bolus of saline, hexarelin or GHRH. Studies were performed following an overnight fast. Each subject underwent six studies performed in a random order and separated by at least 2 days. METHODS Six healthy adult males (23.8-34.3 years) were studied. METHODS Serum GH and IGF-I levels were measured by radioimmunoassay. RESULTS The peak serum GH response to hexarelin was greater than that to GHRH, irrespective of whether the first bolus was saline (P < 0.05) or rhGH (P < 0.02). Prior administration of rhGH led to a reduction in peak serum GH response to hexarelin or GHRH (P < 0.05); the percentage reduction in response to hexarelin was less than that to GHRH, but this difference was not statistically significant (P = 0.3). There was no change in serum IGF-I concentration before or 90 minutes after the administration of rhGH. CONCLUSIONS Hexarelin is a potent GH secretagogue subject to partial feedback inhibition by rhGH. This raises issues about its mechanism of action and may have implications for its potential therapeutic use.