Aims A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery. Methods An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1(st) day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence. Results The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k(21)), but it also increased losses of fluid from the kinetic system (k(b)). The balance between k(21) and k(b) maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k(10)) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates. Conclusions There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.