In hepatobiliary disease and biliary obstruction, bilirubin often becomes covalently bound to albumin circulating in serum, producing a nondissociable complex. To determine how long this complexed bilirubin remains in the circulation, we compared the metabolic clearance of bilirubin-albumin complexes with the clearances of free bilirubin and unmodified albumin. Radiolabeled bilirubin, albumin, and covalent bilirubin-albumin were injected into the circulation of Sprague-Dawley rats and serial samples of plasma were analyzed for the injected compounds. The half-life of bilirubin was 6.2 min. The half-life of bilirubin covalently bound to rat serum albumin was 1.9 to 2.1 days, identical to that of unmodified rat albumin. We conclude that bilirubin covalently attached to albumin is maintained in the circulation with the long half-life of albumin rather than the short half-life of bilirubin. Because albumin in humans has a half-life of 19 days, covalent attachment of bilirubin to human albumin could result in persistence of hyperbilirubinemia long after the resolution of disease.