Evidence exists for the localization of the newly identified estrogen receptor beta (ER beta) within the rat paraventricular nucleus (PVN) and supraoptic nucleus (SON), regions which lack ER alpha. Presently, we investigate whether ER beta-like-immunoreactivity (-ir) is found within cells of several major neuropeptide systems of these regions. Young adult Sprague-Dawley rats were ovariectomized (OVX), and 1 week later half of the animals received estradiol-17 beta (E). Dual-label immunocytochemistry was performed on adjacent sections by using an ER beta antibody, followed by an antibody to either oxytocin (OT), arginine-vasopressin (AVP), or corticotropin releasing hormone. Nuclear ER beta-ir was identified within SON and retrochiasmatic SON, and in specific PVN subnuclei: medial parvicellular part, ventral and dorsal zones, dorsal and lateral parvicellular parts, and in the posterior magnocellular part, medial and lateral zones. However, the ER beta-ir within magnocellular areas was noticeably less intense. OT-/ER beta-ir colocalization was confirmed in neurons of the parvicellular subnuclei, in both OVX and OVX+E brains (approximate to 50% of OT and 25% of ER beta-labeled cells between bregma -1.78 and -2.00). In contrast, few PVN parvicellular neurons contained bath AVP-and ER beta-ir. As web, very little overlap aas observed in the distribution of cells containing corticotropin releasing hormone-or ER beta-ir. In the SON, most nuclear ER beta-ir colocalized with AVP-ir, whereas few OT-/ER beta-ir dual-labeled cells were observed. These findings suggest that estrogen can directly modulate specific OT and AVP systems through an ER beta-mediated mechanism, in a tissue-specific manner.