The effect of GHRH in a dose (120 micrograms) thought to produce a maximal GH response was compared with the GH response to insulin-induced hypoglycemia, iv infusion of the hypothalamic neuropeptide galanin (40 pmol/kg.min for 40 min), and a combination of GHRH and galanin in normal men. The median peak serum GH level was 29 mU/L in response to GHRH, 28.9 mU/L in response to insulin hypoglycemia, 17.3 mU/L in response to galanin, and 115.0 mU/L in response to the combination of galanin and GHRH. GH release induced by galanin was completely inhibited by a concomitant somatostatin infusion (50 pmol/kg.min). Thus, galanin increased the peak GH response to GHRH, previously thought to be one of the most powerful stimulants to GH release, more than 3-fold. Since the dose of GHRH used was thought to be maximal and since galanin is reported not to have direct effects on the pituitary, one possible mode of action of galanin would be inhibition of tonic endogenous hypothalamic somatostatin release.