(A) Hepatic output of biliary cholesterol and phospholipids, but not bile salts, as well as ratios of cholesterol/phospholipids and cholesterol/bile salts were significantly reduced in ABCG5(−/−)/G8(−/−) and ABCG8 (−/−) mice compared to those in WT mice fed the lithogenic diet for 56 days. Bile flow was comparable among three groups of mice. (B) There was a dose-dependent increase in mRNA levels and protein concentrations of ABCG5 and ABCG8 in WT mice in response to an increase in dietary cholesterol. (C) Hepatic cholesterol secretion was increased in a dose-dependent manner not only in WT mice, but also in ABCG5(−/−)/G8(−/−) and ABCG8 (−/−) mice although biliary cholesterol output was lower in the latter than in the former. Abbreviations: BS, bile salts; Ch, cholesterol; PL, phospholipids.