We investigated the modulatory role of gonadal steroids on the expression of oxytocin (OT) and vasopressin (AVP) cytoplasmic mRNAs in the paraventricular nucleus and supraoptic nucleus of the osmotically stimulated rat. We chronically administered an oral salt load (2% sodium chloride solution for 5 days) to intact and gonadectomized female and male Sprague-Dawley rats and measured serum sodium, body weight, pituitary content of OT and AVP immunoreactivities, and size and abundance of hypothalamic cytoplasmic OT and AVP mRNA transcripts. Intact and gonadectomized rats that were administered an osmotic challenge developed comparable degrees of hypernatremia and loss of body weight as well as depletion of posterior pituitary stores of OT and AVP. Hyperosmolality induced elongation of the OT and AVP transcripts in intact and gonadectomized animals, but only intact rats had enhanced hypothalamic cytoplasmic OT and AVP mRNA concentrations to this stimulus. Replacement with gonadal steroids restored the up-regulation in OT and AVP gene expression in gonadectomized animals rendered hyperosmolar. The findings support a modulatory role for gonadal steroids in hypothalamic OT and AVP gene expression during osmotic stimulation.