Thirty-two Sprague-Dawley rats were divided into four groups, eight rats per group. Animals were hypophysectomized with removal of both the pars distalis and the neural lobe of the neurohypophysis. Groups of eight rats were euthanized 1, 2, 4 and 8 weeks following hypophysectomy and prepared for routine scanning electron microscopy (SEM) and correlative immunoelectron microscopy employing antisera against arginine vasopressin (AVP). Eight normal rats served as controls. In experimental rats that survived one to eight weeks posthypophysectomy, remarkable neuroanatomical alterations were notable in the median eminence and adjacent third cerebral ventricular lumen. In contrast to normal control rats, large numbers of neurites were observed with SEM to insinuate from the lateral recess into the cerebral ventricular lumen and as early as one week following hypophysectomy they overgrew the apical surfaces of ependymal cells that constitute the lining of the cerebral ventricle. Immunoelectron microscopy revealed that a significant proportion of these neurites were magnocellular in origin in that they harbored AVP-positive neurosecretory vesicles. In addition to large numbers of invading magnocellular neurites, neuronal perikayria with apparent axosomatic synapses were observed to emerge upon the thick feltwork of invading axons, the latter of which appeared to freely terminate within the ventricular lumen. AVP-positive axon profiles were, in addition, seen to terminate upon the basal lamina of portal perivascular spaces in the zona externa of the median eminence. These data are consistent with the idea that following hypophysectomy (to include high stalk section of the neurohypophyseal system), that there is rapid, and dynamic sprouting and regrowth of AVP-positive axons into the adjacent third cerebral ventricular lumen and to the contact zone of the median eminence as well. This phenomenon may represent a compensatory physiological response to injury of the neurohypophyseal system characterized by a highly plastic neuroanatomical reorganization of magnocellular elements which appear to utilize the CSF of the third cerebral ventricle as a functional terminus for the neurocisternal secretion of AVP which ultimately enters the systemic circulation.