Background: Previous studies have demonstrated that neonatal manipulation of oxytocin (OT) has effects on the expression of estrogen receptor alpha (ER alpha) and the central production of oxytocin observed in juveniles ( at weaning, 21 days of age). The goal of this study was to determine whether the effects of neonatal manipulation of OT last into adulthood, and if the effects differ from those observed during the early postnatal period. On the first day of life, prairie voles ( Microtus ochrogaster) received one of three doses of OT (High, 3 mu g; Med, 0.3 mu g; Low, 0.03 mu g), an OT antagonist, or isotonic saline. Another group was handled, but not injected. Then as adults, brains were collected, sectioned, and stained for ERa or OT using immunocytochemistry. Results: In females, treatment with OT increased the expression of ERa immunoreactivity in the ventral lateral septum (0.03 mu g) and the ventromedial nucleus of the hypothalamus and central amygdala ( 0.3 g). In males, OT antagonist increased ERa expression in the bed nucleus of the stria terminalis. There was no apparent effect of OT on the number of cells producing OT in the paraventricular nucleus of the hypothalamus. Conclusion: The current results suggest that neonatal manipulation of OT has long-term organizational effects on the expression of ERa in both males and females. The lack of effect on OT neurons in the paraventricular nucleus suggests that some developmental effects of OT previously observed in weanlings do not persist into adulthood. Developmental effects of OT on ERa patterns were sexually dimorphic, dose-dependent, and site-specific.