A possible feedback of circulating vasopressin (VP) on the expression of its gene in the hypothalamoneurohypophyseal system was studied in rats with depleted stores of neurohypophyseal hormones. The neural lobe of the pituitary gland was disconnected by anterolateral deafferentation of the basal hypothalamus using a Halasz knife cut. One group of lesioned animals was substituted continuously with VP using mini-osmopumps. After 1 week, the lesion had caused a complete disappearance of neurohypophyseal hormones from the neurointermediate pituitary and induced a 2-fold increase in water intake and an increase in plasma osmolality of approximately 7 m0sm/kg. VP mRNA levels of the supraoptic nucleus (SON), paraventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) were measured in punched tissue by Northern blot analysis and dot-blot analysis. VP mRNA levels of the SON and PVN were reduced by 50% due to the deafferentiation, which might have been caused by degeneration. VP substitution of the lesioned animals normalized water intake but not plasma osmolality. In the VP-substituted animals, VP mRNA levels of the SON were 2-fold reduced compared to the nonsubstituted lesioned animals. The VP mRNA levels of the PVN were not affected by VP substitution. The VP mRNA levels of the SCN increased 2-fold after the lesion but were not influenced by VP substitution. Concomitant determination of oxytocin (OT) mRNA showed that OT mRNA levels in the PVN and SON were not affected by the deafferentiation and did not respond to VP substitution.(ABSTRACT TRUNCATED AT 250 WORDS)