We previously described a colocalization between arginine vasopressin (AVP) and the chemokine Stromal cell-Derived Factor 1 (SDF-1) in the magnocellular neurons of both the hypothalamic supraoptic (SON) and paraventricular nucleus (PVN) as well as in the posterior pituitary. SDF-1 physiologically affects the electrophysiological properties of AVP neurons and consequently AVP release. In the present study we confirm by confocal and electron microscopy that AVP and SDF-1 have a similar cellular distribution inside the neuronal cell and can be found in dense core vesicles in the nerve terminals in the posterior pituitary. Because the Brattleboro rats represent a good model of AVP deficiency, we tested in these animals the fate of SDF-1 and its receptor CXCR4. We identified by immunohistochemistry that both SDF-1 and CXCR4 immunoreactivity were strongly decreased in Brattleboro rats and were strictly correlated with the expression of AVP protein in SON, PVN and the posterior pituitary. We observed by real time PCR an increase in SDF-1mRNA in both heterozygous (HZ) and homozygous (DI) rats. The effect on SDF-1/CXCR4 system was not linked to peripheral modifications of kidney water balance since it could not be restored by chronic infusion of deamino-8D-ariginine-vasopressin, an AVP V2-receptor agonist. These original data further suggest that SDF-1 may play an essential role in the regulation of water balance.