ObjectiveTo determine the relative distribution of fluid within the extracellular fluid volume (ECFV) after infusing either normal saline or 5% albumin in septic, critically ill patients.DesignProspective, randomized, unblinded, interventional study.SettingIntensive care unit in a 450-bed, tertiary care, teaching hospital.PatientsSeptic, critically ill patients (n = 18).InterventionsInfusion of either normal saline or 5% albumin to a hemodynamic end point determined by the patient's clinician.Measurements and Main ResultsPlasma volume (PV), ECFV, cardiac index, and arterial oxygen content were measured immediately before (baseline) and after each fluid infusion. PV and ECFV were measured by dilution of131I-albumin and35S sodium sulfate, respectively. Interstitial fluid volume (ISFV) was calculated as ECFV - PV. Baseline values for PV, ISFV, ECFV, and oxygen delivery index did not differ between treatment groups. Infusion of normal saline increased the ECFV by approximately the volume infused, and the expansion of the PV to ISFV was in a ratio of 1:3. Infusion of 5% albumin increased the ECFV by double the volume infused, with both the PV and ISFV expanding by approximately equal amounts. Oxygen delivery index did not increase after either infusion due to the effect of hemodilution.ConclusionExpansion of the ECFV in excess of the volume of 5% albumin infused suggests that fluid may move from the intracellular fluid volume to the ECFV in septic patients who receive this fluid. (Crit Care Med 1999; 27:46-50)