BACKGROUND By using undenatured purified albumin preparations radiolabeled with iodine, the half-life of serum albumin in well patients who are stable is known to be approximately 17 days. However, when a patient is suffering with an acute illness such as sepsis, trauma, burns or after an extensive operative procedure, the serum albumin level decreases. It is not known whether this fall in serum albumin is due to increased catabolism, decreased synthesis, or a combination of both factors. This study explores the kinetics of albumin catabolism under these circumstances to clarify the issue. METHODS 125I-labeled albumin was administered intravenously to 10 critically ill, hypoalbuminemic patients receiving total parenteral nutrition (TPN). Each subject had frequent blood samples taken for at least 10 days to measure the decline of plasma radioactivity over time. None was receiving unlabeled albumin during the investigation. It was assumed that the plasma decay would follow first-order kinetics after the early equilibration phase. Radioactivity of heparinized blood samples (counts/2 mL sample) were counted and the results were graphically expressed. RESULTS One subject was not evaluated because he was discharged on the 8th day. The APACHE (acute physiology and chronic health evaluation) score for the other nine subjects ranged from 4 to 18 (mean, 7.5). The serum albumin remained below 3.0 g/dL in each subject and did not change statistically throughout the study. The radioiodinated albumin half-life ranged from 5.52 to 11.76 days (mean 9.10 days; compared with published normal of approximately 17 days). The equilibration time was 3 to 7 days. The average albumin catabolized for this group is similar to previously reported normal subjects, 0.18 g/kg/d. CONCLUSIONS Hypoalbuminemic patients receiving TPN have markedly shortened plasma albumin half-lives, but the albumin catabolized per day is similar to normal patients. These data argue for both a synthetic and catabolic defect that explains the hypoalbuminemia in this patient group.