The understanding of fluid changes during hemodialysis (HD is essential for reducing complications as well as efficacy of the procedure. Bioimpedance spectroscopy provides a non invasive method of measuring total body water (TBW), the distribution of intra (ICF) and extracellular (ECF) fluids, and their changes during HD. Segmental bioimpedance may be used to measure the same fluid shifts but from different body segments; the technique has previously been shown to com pare well with whole body measures. It is possible that fluid shifts occur differently in different body compartments during HD. Based on previous hemodynamic studies we postulated that during HD ultrafiltration (UF) the body attempts to preserve its central blood volume (cardiopulmonary circula tion plus great vessels), and thus fluid shifts would be greater from the periphery than from central compartments. To test this hypothesis, segmental bioimpedance (Xitron Technolo gies, San Diego, CA) was performed on 11 subjects undergoing HD where ECF and ICF values were obtained from the legs, arms and trunk before and after a period of UF. Blood volume change (ABV%) was also followed using an on-line optical hematocrit (Hct) sensor (Crit-Line monitor, In-Line Diagnostics, UT) where deltaBV% = deltaBV% = (1 - Hct1/Hct0) x 100 (Hct0 = baseline Hct; Hct1 = postultrafiltration Hct) The UF of 2.0 L +/- 0.79 L (M +/- SD) over 75 minutes was associated with a deltaBV% of -9.43% +/- 3.6% (M +/- SD), a significant (Student's paired t-test) reduction in total body (TB) ECF (p < 0.02), a weak correlation in reduction in TBW (p = 0.09) but not in TB ICF. The ECF reductions from the trunk, legs, and arms were all significant (minimum p < 0.02); no ICF changes from these compartments were significant. The amount of ECF reduction was greater from the legs (0.7 L +/- 0.6 L) than the arms (0.12 L +/- 0.08 L) and trunk (0.2 L +/- 0.2 L) (all M +/- SD). Multiple regression analysis showed that TB ECF changes correlated strongly with leg (r = 0.94, p < 0.001) and arm (r = 0.72, p = 0.002) ECF changes but not with trunk changes. deltaBV% correlated weakly with leg (r = 0.45, p = 0.08) and arm (r = 0.42, p = 0.10) ECF changes but not with the trunk. As the deltaBV% represents the net volume change between UF and plasma water refilling, thiss indicates that plasma water is being removed more from the peripheral compartments than from the trunk. These data suggest that plasma refilling during HD to preserve central blood volume is more dynamic from the leg ECF than from elsewhere and may, in turn, explain the frequent occurrence of leg cramps during and after hemodialysis.