Circulation blood volume can be estimated with the initial distribution volume of glucose (IDVG) method. In a prospective, observational study, we evaluated the effect of a fluid challenge on IDVG in individual patients. In 13 patients after cardiac surgery, IDVG was determined before and after the infusion of 7 mL/kg hydroxyethyl starch over 30 min. Eleven patients not requiring a fluid challenge served as control. IDVG was computed with a one-compartment exponential model, using plasma glucose concentrations at baseline and 3, 4, 5, 6, and 7 min after 5 g of glucose IV bolus. IDVG was repeated 3 times in the control group. IDVG did not change after a fluid challenge (85 +/- 14 versus 93 +/- 14 mL/kg, P = 0.08), and the power of the comparison was 0.25 for a P value of 0.05. The regression coefficient of the exponential fit of glucose versus time was 0.96 +/- 0.03 before, and 0.95 +/- 0.04 after starch infusion (not significant). In the control group, IDVG was 90 +/- 18 mL/kg, and the average individual coefficient of variation was 0.15 +/- 0.08. IDVG seems inadequate to assess individual response to fluid therapy. This limitation may be related to the weak reproducibility of IDVG. IMPLICATIONS: The initial distribution volume of glucose (IDVG) is supposed to reflect effective circulating blood volume. We assessed the sensitivity of this method to a fluid challenge in patients receiving a fluid challenge, and the reproducibility in otherwise stable patients. IDVG was not sensitive to a fluid challenge, and reproducibility was poor. Thus, clinical usefulness of IDVG seems limited.