Endotoxin has been shown to stimulate ACTH and cortisol secretion through an action at the hypothalamic level. However, the nature of hypothalamic neurohormones, corticotropin-releasing hormone (CRH) and especially arginine vasopressin (AVP), involved in that regulation is still controversial. The purpose of this study was to determine the effects of an acute i.v. endotoxin administration on CRH and AVP secretion into hypophysial portal blood (HPB). The experiment has been performed in sheep since it is possible to collect HPB and quantify CRH and AVP secretion in this animal under physiological conditions. The release of both peptides into HPB was stimulated by endotoxin injection, the increase in portal AVP being more pronounced than that of CRH. An initial, transient, increase in jugular AVP concentrations was observed, probably due to the activation of magnocellular AVP neurons. In conclusion, our data indicate that the activation of the pituitary-adrenal axis after endotoxin injection is associated with an increased release of both CRH and AVP into HPB. Magnocellular AVP neurons are initially stimulated while parvocellular CRH and AVP neurons are stimulated throughout the experiment.