Infusions of hyperosmotic-hyperoncotic solutions such as hypertonic saline dextran (HSD) are used in Europe for resuscitation of traumatic shock and perioperative volume support as an adjunct to conventional isotonic crystalloids. Whereas plasma volume expansion of HSD has been measured at single time points after the intravascular volume expansion, the detailed time course of fluid shifts during and after infusions have not been reported. We compared the time course of volume expansion during and after 30-min infusions of 4 mL/kg HSD and 25 mL/kg lactated Ringer’s solution (LR) in normovolemic conscious splenectomized sheep. Peak plasma volume (Evans blue and hemoglobin dilution) expansion was similar for HSD (7.8±0.9 mL/kg) and the larger sixfold volume of LR (7.2±0.5 mL/kg). However, 30 min after the 30-min infusion (T60), plasma expansion remained larger after HSD (5.1±0.9 mL/kg) than after LR (1.7±0.6 mL/kg). Both solutions caused an equivalent diuresis. Intravascular volume expansion efficiency (VEE), defined as milliliter plasma expansion/milliliter fluid infused at 0 (T30), 30 (T60), and 60 (T90) min after infusion ended was 1.8, 1.3, and 0.8, respectively for HSD, whereas LR provided a VEE of only 0.27, 0.07, and 0.07. The relative expansion efficiency of HSD versus LR, calculated as the ratio (VEE HSD/VEE LR), was 7-fold that of LR at the end of infusion T30, and 20-fold at T60, but decreased to 9-fold by T120. Intravascular volume dynamic studies of different volume expanders in animals and patients may provide anesthesiologists with a new tool for monitoring the effectiveness of fluid therapy.