Abstract While extensive evidence suggests that adrenoceptors play an important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra- and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCI-depolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat GHRH(1-43) on high-performance liquid chromatography and Sephadex G-75 chromatography. Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range 10(-10)- 10(-6)M, with a plateau in response at 10(-7)M. Stimulation with noradrenaline 10(-7)M was blocked by idazoxan 10(-5)M and attenuated by thymoxamine 10(-5)M, but was unaffected by timolol 10(-5)M. Both the alpha(2)-adrenoceptor agonist guanfacine, and the alpha(1)-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion. It is concluded that noradrenaline stimulates the release of GHRH at both alpha(1) and alpha(2)-adrenoceptors.