In conscious rats with near-malignant phases of DOCA-salt (DS) hypertension, hemodynamics were studied with microspheres before and after administration of a vasopressin (VP) vasopressor antagonist in relation to plasma VP levels (pVP). Compared to the controls, the DS rats showed significant elevations in mean arterial pressure (MAP), total vascular resistance (TVR), and pVP, and a flow redistribution from kidney and spleen to skeletal muscles and heart, with increased vascular resistance in almost all organs. The antagonist elicited no significant systemic hemodynamic effects in DS rats as a whole; however, two subgroups, responders vs nonresponders, were identified according to the effects on MAP. In responders with a pVP of 29.2 ± 2.7 (SE) pg/ml, the antagonist lowered MAP (− 24.9 ± 5.9 mm Hg) and TVR significantly, while in nonresponders with a pVP of 15.2 ± 3.4 pg/ml, there were no effects. The major antagonist-induced regional responses were increased flow and decreased vascular resistance in skeletal muscles and skin in whole DS rats, and additionally in the gastrointestinal tract, portal organs, and testes in the responders. Significant correlations were observed between pVP, MAP, TVR, and depressor responses to the antagonist only when all data for DS and control rats were pooled. Thus, the systemic hemodynamic effects of VP are important only in responders with exceedingly elevated pVP. VP contributes significantly to the regional hemodynamic abnormalities in skeletal muscles and skin in whole DS rats, and also in several other organs in the responders.