BACKGROUND: Albumin may persist intravascularly for a shorter time in patients after major surgery than in healthy volunteers due to a surgery-induced breakdown (shedding) of the endothelial glycocalyx layer. METHODS: In this nonrandomized clinical trial, an IV infusion of 3 mL/kg of 20% albumin was given at a constant rate during 30 minutes to 15 patients on the first day after major open abdominal surgery (mean operating time 5.9 h) and to 15 conscious volunteers. Blood samples and urine were collected during 5 h and mass balance calculations used to estimate the half-lives of the administered albumin molecules and the induced plasma volume expansion, based on measurements of hemodilution and the plasma albumin concentration. RESULTS: At the end of the infusions, albumin had diluted the plasma volume by 13.3% +/- 4.9% (mean +/- SD) in the postoperative patients and by 14.2% +/- 4.8% in the volunteers (mean difference -0.9, 95% CI, -4.7 to 2.9; 1-way ANOVA P = .61), which amounted to twice the infused volume. The intravascular half-life of the infused albumin molecules was 9.1 (5.7-11.2) h in the surgical patients and 6.0 (5.1-9.0) h in the volunteers (Mann-Whitney U test, P = .26; geometric mean difference 1.2, 95% CI, 0.8-2.0). The half-life of the plasma volume expansion was 10.3 (5.3-17.6; median and interquartile range) h in the surgical patients and 7.6 (3.5-9.0) h in the volunteers (P = .10; geometric mean difference 1.5, 95% CI, 0.8-2.8). All of these parameters correlated positively with the body mass index (correlation coefficients being 0.42-0.47) while age and sex did not affect the results. CONCLUSIONS: Twenty percent albumin caused a long-lasting plasma volume expansion of similar magnitude in postoperative patients and volunteers.