Considerable circumstantial evidence has now accumulatedto indicate that monohydroxy bile acids such as lithocholi acid (3a-hydroxy-5~-cholanoic acid) and 3/3-hydroxy-5- chenodeoxycholic acid  are of endogenous origin (1-3) and are found inbiologic fluids beginning in fetal life (4-6). Because in the adult the major source of lithocholic acid is known to be frombacterial dehydroxylation of chenodeoxycholic acid (3a,7adihydroxy-5P-cholanoicacid), recognition that it can also be synthesized in the liver was not appreciated. However, lithocholicacid has been found to occur in the newborn period independent of intestinal bacterial activity (7) chenodeoxycholic acid is consonantwith the knowledge that it is derived from 3P-hydroxy-5-cholenoic acid in vivo in the hamster (8) and the knowledgethat in humans the latter bile acid has been shown to be
derived from radioactive cholesterol (5-cholesten-3/3-01) given parenterally (1, 2).More recent studies also indicate that esterification of these monohydroxy bile acids with sulfate or the formation of
glucuronides does not eliminate their deleterious biologic effects(9, IO), and therefore hydroxylation to chenodeoxycholic acid is essential.
Although we previously thought that metabolism to chenodeoxycholic acid was via lithocholic acid (ll), our curren findings in humans and rabbit indicate that a different pathwaymust exist in these species. Moreover, by using radioactivelithocholic acid and 3P-hydroxy-5-cholenoic acid