We studied the effect of standardized ultrafiltration (UF, 2 liters in 60 min) on plasma volume (PV, 131I-albumin space) and its recovery, with special reference to the tissue hydration before UF. Twenty-one UF sessions were performed in 15 patients with endstage renal failure. The PV reduction, which varied considerably, was maximal at the end of UF (range, -0.7 to -21.9%); after that PV recovered reaching a plateau in the second hour after UF. A highly significant negative correlation was found between the interstitial fluid volume (IVF, calculated from 82Br space-PV) and the PV reduction at this stage (r = -0.89, P less than 0.0001). Despite avoidance of major changes in total extracellular fluid in the next 24 hr, a further restoration of PV took place which was partial in subjects with normal tissue hydration, but complete or even excessive in grossly overfilled subjects. This PV repletion was accompanied by an increase in the intravascular mass of albumin (P less than 0.02). The negative correlation between initial IFV and PV change persisted after 24 hr (r = -0.83, P less than 0.0005). In most occasions the blood pressure fell, but only in eight occasions frank hypotension followed. Heart rate remained remarkably unaltered, even during hypotensive episodes. Changes in plasma renin activity followed no uniform pattern. Our findings indicate that the tissue hydration state has a strong influence on changes in PV during fluid removal and the subsequent repletion of PV.