Volume overload is a factor in development of hypertension in hemodialysis patients. Fluid removal by hemodialysis (HD), however, may cause intradialytic hypotension and associated symptoms. A better understanding of the relationships between blood pressure volume status and the pathophysiology of fluid removal during HD are, therefore, necessary to control blood pressure and to eliminate intradialytic hypotension. The objectives of the study were to determine the amount and direction of change of body fluid compartments after ultrafiltration (UF) and to determine whether any correlations exist between mean arterial pressure (MAP), change in circulating blood volume (deltaBV), total body water (TBW), central blood volume (which constitutes the volume of blood in the lungs, heart, and great vessels [CBV]), and intracellular and extracellular fluid volumes (ICF, ECF). The study population included 20 patients on regular HD. Each individual had their CBV, cardiac output, and peripheral vascular resistance (PVR) measured by means of saline dilution technique and deltaBV monitored by an online hematocrit sensor (Crit Line). MAP was calculated from measured blood pressure and ICF and ECF were measured using bioelectric impedance analysis techniques. Measurements were obtained before and after maximum UF measured by deltaBV (reduction of 6-10% by Crit Line). Ten healthy controls also had ECF and ICF values measured by bioelectric impedance analysis. Before HD, MAP correlated with TBW (r = 0.473, p = 0.035) and CBV (r = 0.419, p = 0.066), suggesting that hypertension here may be due to volume overload. Patients were ECF expanded before HD with an ECF:ICF ratio of 0.96, which was significantly higher than the control ratio of 0.74 (p < 0.0001). During UF, fluid was removed from both ECF and ICF, but more from the ECF volume ratio 0.92 post UF, a significant reduction (p < 0.0001). After UF, MAP no longer correlated with TBW or CBV but correlated with peripheral vascular resistance (r = 0.4575, p = 0.043). After UF, deltaBV correlated inversely with PVR (r = -0.50, p = 0.024). Despite the fall in deltaBV (7.11+/-2.49%) with UF, CBV was maintained. CBV were 0.899 L and 0.967 L pre and post UF, respectively. These data suggest that in hemodialysis patients, predialysis volume status influences predialysis blood pressure. UF causes BV to fall, but CBV is preferentially conserved by increasing PVR, which also maintains blood pressure. Failure of a PVR response likely leads to intradialytic hypotension.