SUMMARY Experiments were performed to determine the role of vasopressin in deoxycorticosterone (DOC)-salt hypertension. In order to determine if vasopressin is necessary for the development of DOC-salt hypertension, rats with hereditary diabetes insipidus (DI) and normal Long-Evans rats (LE) were unilaterally nephrectomized, treated with DOC Pivalate (30 mg/kg week) and given saline to drink for 8 weeks. A second group of DI rats were unilaterally nephrectomized, but received no treatment. Systolic blood pressure (SBP) increased 40 mm Hg in the LE group (p < 0.01) but failed to increase significantly in either DI group. Urinary excretion of vasopressin (U ADH V) and SBP were measured in unilaterally nephrectomized LE rats treated with DOC and salt (DOC-LE), salt alone (NaCI-LE) and untreated rats (H.O-LE). The UADHV was elevated in DOC-LE (j> < 0.01) and NaCI-LE (p < 0.05) rats, but only the DOC-LE rats became hypertensive. Finally, the I.V. injection of analogs of vasopressin, which block its pressor but not antidluretic activity, lowered mean arterial blood pressure 27 ± 5 mm Hg in 11 conscious DOC-salt hypertensive rats. It is concluded that vasopressin plays a major role as a pressor agent in both the onset and maintenance of DOC-salt hypertension.