Growth hormone-releasing hormone was isolated 1982 from human pancreatic tumours. They were found to consist of three peptides (GHRH1-44, GHRH1-40, GHRH1-37) which in vivo and in vitro were specific stimulators of pituitary growth hormone secretion. These tumor-derived GHRHs were demonstrated to be identical to human hypothalamic GHRHs. Extrahypothalamic GHRH is present in some brain regions and in the gastrointestinal tract. Circulating GHRH is detectable in human plasma, but little is known about its function. Above all binding of GHRH to a specific receptor stimulates growth hormone secretion through formation of cyclic AMP. GHRH secretion is modulated by somatostatin, the somatomedins and growth hormone itself. Following single injection of GHRH1-44 i.v. the equilibration half-time is 1.0 +/- 0.2 min and elimination half-time is 6.8 +/- 1.2 min. Maximal growth hormone response is achieved after injection of 1 microgram/kg GHRH. Using higher GHRH-doses growth hormone can be stimulated via subcutaneous or intranasal application. A single i.v. GHRH-test is not sufficient to prove a pituitary defect since growth hormone can be stimulated following repetitive injections in some cases. About 50% of patients with growth hormone deficiency have a hypothalamic defect of GHRH release. In some of these patients GHRH s.c. can promote linear growth to the same degree as growth hormone treatment.