Studies were performed to characterize the regulation of central vasopressin (AVP) receptors in deoxycorticosterone acetate (DOCA)-NaCl-treated and control rats, and in DOCA-treated primary neuronal enriched cell cultures. Uninephrectomized rats were given NaCl to drink and implanted subcutaneously with a silastic implant containing 200 mg/kg DOCA. [3H]AVP binding to a diencephalic block of tissue was examined. Whereas DOCA-NaCl treatment did not affect the affinity of [3H]AVP binding, the total number of AVP receptors was increased between 3 and 14 days following DOCA-NaCl administration. No differences in the number of binding sites were present in the established (35-56 days after DOCA-NaCl administration) stages of hypertension. To determine whether the increase in [3H]AVP binding was a direct effect of DOCA on neurons or related to the hormonal, volume or other physiologic changes that DOCA-NaCl treatment causes in the whole animal, [3H]AVP binding was examined in neurons grown in culture that was treated with DOCA. Scatchard analysis demonstrated that DOCA treatment (compared to control) produced an increase in the number but no change in the affinity of the AVP binding sites in primary neuron-enriched cultures. Treatment of cultured neurons with other steroids (estrogen, corticosterone, or aldosterone), did not change the kinetics of [3H]AVP binding, suggesting that the effects of DOCA on the AVP receptor were specific for this steroid. These data indicate that, in comparison to control rats, DOCA-NaCl hypertensive rats, have an enhanced number of AVP receptors in the diencephalon, perhaps as a direct result of an interaction between DOCA and AVP receptors. Since these changes in AVP binding occur during the early, developmental stage of DOCA-NaCl hypertension, they may contribute to the rise in arterial pressure. © 1991.