The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man. Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary, at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone, and when administered with growth hormone-releasing hormone has a synergistic effect. In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus. We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation. Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area.