A number of changes occur in the oxytocin (OT) system during gestation such as increases in hypothalamic OT mRNA, increased neural lobe and systemic OT, as well as morphological and electrophysiological changes in OT-containing magnocellular neurons, suggestive of altered neuronal sensitivity, which may be mediated by ovarian steroids. Since central norepinephrine (NE) and histamine (HA) are potent stimulators of OT release during parturition and lactation, the present study investigated the effects of central noradrenergic and histaminergic receptor activation on systemic (NE, HA) and intranuclear (NE) OT release in pregnant rats, and in ovariectomized rats treated with ovarian steroids. Plasma OT levels in late gestation were significantly higher compared to all other groups, and neither adrenergic nor histaminergic receptor blockade decreased these elevated levels. Furthermore, the -adrenergic agonist, phenylephrine, but not histamine, stimulated systemic OT release to a significantly greater extent in late gestation than in mid-pregnant, ovariectomized, or steroid-treated females. While basal extracellular OT levels in the paraventricular nucleus, as measured with microdialysis, were unchanged during pregnancy or steroid treatment, noradrenergic receptor stimulation of intranuclear OT release was significantly elevated in mid-gestation females compared to all other groups. These studies indicate that sensitivity of intranuclear and systemic OT release to noradrenergic receptor activation differentially varies during the course of gestation.