The present review is dealing with the five major hypothalamic hypophysiotropic neuropeptides (H.H.N.P.) purified and synthesized so far. Four of them specifically stimulate the secretion of one or several anterior pituitary (A.P.) hormones, i.e. thyroliberin (TRH) on TSH and prolactin, gonadoliberin (GnRH) on LH and FSH, corticoliberin (CRF) on ACTH and precursor peptides and somatocrinine (GRF) on GH. The fifth one, somatostatin (SRIF), inhibits the secretion of all A.P. hormones, excepted LH and FSH. All H.H.N.P. affect, positively or negatively, in a dose- and time-dependent manner, the release of stored hormones and their neosynthesis. These responses are submitted to multihormonal modulations. They are initiated by the occupancy of high affinity specific binding sites which have been extensively characterized and morphologically localized. Informations concerning molecular characterization and cloning of receptors for any H.H.N.P. are still awaited. By contrast, the transduction mechanisms which are activated by the occupation of receptors have been extensively studied. They vary depending on H.H.N.P.: TRH and GnRH activate the catabolism of polyphosphoinositides and ensuing pathways, CRF and GRF activate and SRIF inhibits adenylate cyclase dependent pathways. In addition, Ca2+, from extracellular and intracellular sources, play a pivotal role in all cases. The intracellular mechanisms responsible for the last steps of H.H.N.P. action, i.e. exocytosis of secretory granules and transcription of target genes, are however still unknown.