An important factor in the development of hypotension during hemodialysis (HD) is a decrease in blood volume, due to ultrafiltration (UF) and an insufficient refill of the intravascular compartment. This insufficient refill might be caused by a transcellular fluid shift from the extracellular to the intracellular compartment. We studied the influence of dialysate sodium concentration and UF rate on the refill rate, blood volume, intracellular (ICV) and extracellular fluid volume (ECV). Three different HD strategies were studied in 15 patients: (A) conventional HD (dialysate sodium 140 mmol/L); (B) HD with a sodium profile (140-148 mmol/L); and (C) HD with a sodium profile and a variable UF rate (high-low UF rate). ICV and ECV were measured by non-invasive conductivity measurements, blood volume was calculated from erythrocyte counts before and after treatment. Blood volume decrease was most pronounced during conventional HD, due to insufficient refilling without a detectable transcellular fluid shift. The sum of the decrease in ICV and EVC was less than during (B) and (C). The insufficient refill led to a higher prevalence of hypotension and cramps. The strategies (B) and (C) led to an significant and comparable transcellular fluid shift to the extracellular compartment. Thus, the use of a sodium profile led to a better intravascular refill and clinical tolerance of HD. Addition of a UF profile did not improve this any further.