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Most of the bile pigment excreted under physiologic conditions is derived from hemoglobin of senescent erythrocytes. However, the classic studies of London, West, Shemin, and Rittenberg (2) and of Gray, Neuberger, and Sneath (3) in 1950 indicated that additional sources account for a small but significant fraction of the total pigment production. With glycine-15N as a precursor of hemoglobin heme, it was shown that human erythrocytes containing labeled heme survive for an average of 120 days. As anticipated, most of the labeled bile pigment is formed as these cells leave the circulation and are destroyed. In addition, a smaller fraction of the labeled bile pigment appears within the first few days of isotope administration, when labeled red cells are just beginning to enter the circulation. In normal subjects this "early labeled" pigment (ELP) or "shunt fraction" (4) represents 10 to 20% of the total bile pigment formed from labeled glycine (2, 3). However, in some hematologic disorders, particularly those associated with "ineffective erythropoiesis" (5), the ELP may account for the major portion of the excreted bile pigment (3, 4, 6-13). Several recent investigations concerning the origin of the ELP in hematologically normal subjects and experimental animals have yielded con-

The sources of bile pigment in the rat: studies of the "early labeled" fraction.