Enucleation-induced adrenal regeneration is a classic model to investigate adrenocortical proliferation in vivo, which is dependent not only on pituitary ACTH release, but also on various other neural and endocrine signals. Arginin-vasopressin (AVP), mainly acting via Vi receptors, regulates hypothalamic-hypophyseal-adrenal axis fuction, acting on both its central and peripheral branches. Here, we studied whether endogenous AVP system modulates rat adrenal regeneration. Reverse transcription-polymerase chain reaction (PCR) detected only the mRNAs of Via and Vib receptors in normal and regenerating adrenals. The expression was very low, and semi-quantitative conventional and real-time PCR showed that it was down-regulated in regenerating adrenals in relation to the time elapsed from enucleation. AVP (three subcutaneous injections 28, 16 and 4 h before sacrifice) raised metaphase index at day 5, but not at day 8 of regeneration. Unexpectedly, both Vi-receptor and V-2-receptor antagonists increased metaphase index at days 5 and 8 of regeneration. Neither AVP not AVP-receptor antagonists affected plasma levels of corticosterone in rats bearing regenerating, adrenals. It is concluded that AVP, acting via Vi receptors located in adrenals. exerts a stimulating effects on adrenal regeneration. Due to the down-regulation of Vi-receptor expression in regenerating adrenals, this effect is very weak and is easily overcome by a tonic inhibitory action of endogenous AVP systems probably involving extra-adrenal indirect mechanisms.