To investigate the role of delta-opioid receptors in the modulation of growth hormone (GH) secretion, we compared in normal subjects the effect of the highly selective delta-opioid receptor agonist Deltorphin (DT) on the GH secretion responses to pituitary (GH-releasing hormone, GHRH)- and hypothalamic (insulin-induced hypoglycemia, IIH)-mediated stimuli. DT blunted the GH response to IIH, whereas it had no effect on the GH response to GHRH. It is concluded that in man DT-induced activation of delta-opioid receptors exerts an inhibitory action on hypoglycemia-stimulated GH secretion. Based on the lack of an effect of DT on the GH response to GHRH, we suggest that DT may modulate the secretion of GH through suprapituitary mechanisms.