In the present study, the distribution of P2X receptor protein and colocalization of P2X receptors with vasopressin and oxytocin in the supraoptic and paraventricular nuclei of rat hypothalamus was studied using double-labeling fluorescence immunohistochemistry. The results showed that vasopressin-containing neurons expressed P2X(2), P2X(4), P2X(5) and P2X(6) receptor and oxytocin-containing neurons expressed P2X(2), P2X(4) and P2X(5) receptors in the supraoptic nucleus. In the paraventricular nucleus, vasopressin-containing neurons expressed P2X(4), P2X(5) and P2X(6) receptors, while oxytocin-containing neurons expressed P2X(4) receptors. This study provides the first evidence that P2X receptor subunits are differentially expressed on vasopressin- and oxytocin-containing neurons in the supraoptic and paraventricular nuclei, and hence, provides a substantial neuroanatomical basis for possible functional interactions between the purinergic and vasopressinergic systems, and the purinergic and oxytocinergic systems in the rat hypothalamus.