To investigate the possible role of vasopressin (VP) in the maintenance of DOC-salt hypertension the effect of two VP pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous VP were studied in conscious, freely moving rats with malignant DOC-salt hypertension. Intravenous injections of either 20 micrograms/kg of dP Tyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP had no significant effect on mean arterial pressure and heart rate, although both antagonists almost completely abolished the pressor response to VP. Furthermore, the animals with DOC-salt hypertension exhibited decreased pressor responsiveness to exogenous VP. The present findings strongly suggest that VP is not essential as a pressor hormone for maintaining blood pressure in malignant DOC-salt hypertension.