We used a structural analogue of arginine vasopressin (AVP) and investigated the role of AVP in the maintenance of mean arterial pressure (AP) in anesthetized, water-deprived rats. The administration of [1(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 4-valine-8-D-arginine] vasopressin, d(CH2)5VDAVP, completely inhibited to 30-40 mma Hg rise in AP which normally accompanied the administration of 50 mU exogenous AVP (group 1). Thus, d(CH2)5VDAVP is a specific antagonist of the vascular effects of AVP. d(CH2)5VDAVP failed to significantly alter AP in water diuretic rats (group 3) and was without effect on urine osmolality during water diuresis or antidiuresis. However, bolus injection of d(CH2)5VDAVP into water deprived rats (group 2) prompted an abrupt fall in AP from 112 +/- 4 to 94 +/- 4 mm Hg (P less than 0.001). This fall in AP was transient, with return of AP to 110 +/- 4 mm Hg within 15 minutes. Administration of saralasin, an angiotensin II antagonist, not only prevented the compensation in AP, but also significantly magnified the maximal hypotensive response seen following d(CH2)5VDAVP (group 4). Discontinuing the saralasin allowed AP to return to baseline. Bilateral nephrectomy (group 5) also prevented the return of AP, further implicating endogenous angiotensin II as the specific mediator of the compensation in AP following d(CH2)5VDAVP administration. These studies clearly demonstrate that circulating AVP contributes to the maintenance of AP during water deprivation in the anesthetized rat. When this vascular action of AVP is blocked, angiotensin II assumes major responsibility for blood pressure regulation in the antidiuretic state.