To investigate the possible role of body fluid volume or the renin-angiotensin system in the maintenance of high blood pressure in chronic one-kidney, one clip (1K1C) hypertension, we studied whether blood pressure remained high after removal of the clip while the body fluid volume was kept constant or when angiotensin II (Ang II) was infused in conscious 1K1C rats. Blood pressure fell 58 +/- 13 mm Hg in 1K1C rats after removal of the clip. When body fluid volume was kept at the same level as before "unclipping," blood pressure fell only 9 +/- 2 mm Hg after removal of the clip; if body fluid volume was then allowed to decrease, blood pressure fell an additional 55 +/- 8 mm Hg. When Ang II was infused after removal of the clip, blood pressure fell 26 +/- 7 mm Hg despite the fact that plasma Ang II increased to nonphysiological concentrations (1,161 +/- 353 pg/ml). After Ang II infusion was stopped, blood pressure fell an additional 44 +/- 13 mm Hg. When Ang II was infused and body fluid volume kept constant, blood pressure still did not change after removal of the clip, although plasma Ang II concentrations increased to nonphysiological levels (618 +/- 98 pg/ml). After the Ang II infusion was discontinued and the body fluid volume was no longer kept constant, blood pressure fell 78 +/- 9 mm Hg. These data further support the hypothesis that a volume factor, not the renin-angiotensin system, is important in the maintenance of high blood pressure in 1K1C hypertension.