We have investigated the effects of lesioning the hypothalamic paraventricular nucleus (PVN) on the secretion of two corticotropin-releasing neurohormones, vasopressin (VP) and oxytocin (OT), at the median eminence. The experimental model was the median eminence incubated in vitro, the secretion of neurohormones was stimulated by adding 48 mM KCl to the incubation medium. In addition, immunohistochemical staining was performed to correlate the changes in neuropeptide secretion with the distribution of VP and OT immunoreactive elements in the median eminence. Lesioning of the PVN abolished the KCl-induced release of VP 1 week after hypothalamic surgery. After a longer period of postoperative survival (6 weeks), VP release was restored towards normal. The secretion of OT was reduced by 50% at 1 week after lesioning and rose to 400% of control at six weeks. The changes in VP and OT release at the median eminence largely correlated with the immunohistochemical distribution of VP and OT immunopositive nerve fibers in the external zone of the median eminence. Most importantly, 6 weeks after the PVN lesion a dense network of OT immunoreactive varicosities was observed around primary portal capillaries, where normally OT fiber density is very low. These results demonstrate the functional and structural plasticity of VP- and OT-ergic neuronal systems that project to the median eminence. Furthermore, when taken together with earlier studies on the regulation of corticotropin secretion in long-term PVN-lesioned rats, the data indicate an important role for OT in the regulation of pituitary-adrenocortical function in PVN-lesioned rats.