1. [3H]Bilirubin and 131I-labelled albumin were given simultaneously to six healthy adults by intravenous route and the amounts in the plasma were measured for several days. Multicompartmental analysis of the data showed that the rate of movement of [3H]bilirubin from the plasma into the extrahepatic extravascular space was 29·7 ± 7·3% (mean ± SEM) of the plasma pool/h, whereas the rate of movement of 131I-labelled albumin from plasma into the extravascular space was only 7·2 ± 1·0% of the plasma pool/h.
2. [14C]Bilirubin was found to equilibrate throughout the body of a child with the Crigler-Najjar syndrome within 24 h of intravenous administration, whereas 131I-labelled albumin required 4–5 days in human subjects.
3. Multicompartmental analysis of the plasma data in the six healthy adults indicated that the mass of material in the extrahepatic extravascular space relative to that in plasma was greater for unconjugated bilirubin than for albumin.
4. Studies of the tissue distribution of unconjugated bilirubin in homozygous Gunn rats demonstrated that the organs which comprise the rapidly exchanging extravascular albumin pool (liver, kidney and intestine) accumulated unconjugated bilirubin in excess of their albumin content, whereas lesser amounts of unconjugated bilirubin were accumulated in the tissues which make up the slowly exchanging extravascular albumin pool (muscle, fat and skin).
5. These findings indicate that unconjugated bilirubin moves more rapidly between plasma and extrahepatic extravascular sites than can be accounted for by transport bound to albumin. They also indicate that extravascular binding of unconjugated bilirubin includes tissue sites, as well as extravascular albumin.