Whole body bioimpedance is considered helpful in monitoring the removal of excess body water by ultrafiltration in hemodialysis patients. In this study, the cumulative, estimated decrease in extracellular volume (Vest) modeled from whole body bioimpedance data was compared with measured volume (Vmeas) removed by ultrafiltration (UFR = 1.01 ± 0.31 L/hr) in 12 patients during 36 high efficiency hemodialysis treatments. In the mean, estimated (Vest=3.0 ± 1.4 L) and measured volumes (Vmeas=3.4 ± 1.1 L) correlated linearly: Vest = 1.05 x Vmeas − 0.60, r2 = 0.68. Patients developed hypotension in half the treatments. Except for a larger decrease in systolic blood pressures in hypotensive (34 ± 24 mmHg) vs. stable (14 ± 15 mmHg) treatments, patient and treatment characteristics were not different between groups. However, at the end of hemodialysis, the difference Vest − Vmeas was − 0.8 ± 0.9 L in hypotensive, and only 0.1 ± 0.4 L in stable patients (p < 0.05). The difference between Vest and Vmeas can be explained by a predominant removal of excess body water from central body compartments such as the trunk and the central blood volume during hypotension. These compartments are not adequately measured by whole body bioimpedance techniques. However, this information could be helpful in identifying patients with delayed peripheral fluid removal that may occur when either target weight is too low or UFR rates are too high.