The rodent hypothalamic neurosecretory system normally exhibits remarkable functional and structural plasticity following injury. However, the present study describes a newly observed phenomenon in which neurohypophysectomized animals receiving chronically administered exogenous vasopressin during the post-lesion period (a treatment which insures maximal renal antidiuresis over this time frame) lose all capacity for recovery of antidiuretic function. Functional deficits are accompanied by a severe reduction in the number of neurons exhibiting immunohistochemical staining for arginine vasopressin. These data indicate that the presence of neurological stimulation signaling vasopressin release may play an important role in promoting neural regeneration of the vasopressinergic component of the neurosecretory system.