To elucidate the effects of albumin on the handling of serum bilirubin, hepatic metabolism and biliary excretion of bilirubin were examined during intravenous bilirubin infusion in Sprague-Dawley (SD) rats, Gunn (heterozygous, Jj) rats, and Nagase analbuminemic rats (NARs). Serum bilirubin was primarily bound to a protein fraction with a molecular weight of about 600 x 10(3) or more in NARs. About 39.2% +/- 12.5% of the serum bilirubin during infusion of bilirubin was bound to the same fraction in Gunn rats. Bilirubin was substantially taken up into the liver and excreted into the bile in NARs, suggesting the role of a high molecular protein, probably a lipoprotein, in its blood transport and the hepatic uptake process. In NARs, biliary bilirubin secretion reached the peak between 20 and 40 minutes after the initiation of bilirubin loading and decreased thereafter, whereas it continued to increase in SD rats and in NARs to which albumin was administered 20 minutes after the start of bilirubin loading. Biliary bilirubin fractions before bilirubin loading were similar in SD rats and NARs, whereas an increase in bilirubin monoglucuronide (BMG) and a decrease in bilirubin diglucuronide (BDG) were observed in Gunn rats. After the initiation of bilirubin loading, a decrease in biliary BDG and an increase in BMG and unconjugated bilirubin were observed in all groups of rats.