Hypothetical condensed phase diagram for gallbladder bile of mice that represents an estimate for an equimolar taurocholate–tauro-β-muricholate mixture (11, 12). The division of the phase diagram for gallbladder bile of ∼7.3 g/dL lipids (37°C) above the micellar zone is interpolated from published phase diagrams for both pure taurocholate and the pure hydrophilic bile salt tauroursodeoxycholate, each with natural (egg) phosphatidylcholine and cholesterol (11). However, it takes into consideration that β-muricholate (the taurine conjugate representing 50% of the bile salt pool in ref. 2) displays approximately half the solubility of ursodeoxycholate for cholesterol (8, 24). Above the small micellar zone are, from left to right, two-, three-, and two-phase regions, each of which contains mixed micelles and separated phases which are indicated schematically on the figure. Relative lipid compositions of Yu et al.’s (2) littermate control mice (open circles, females; open squares, males) plot just above the micellar zone, indicating that they are slightly supersaturated with cholesterol. However, biles of the transgenic animals (closed circles, females; closed squares, males) are markedly enriched in cholesterol (2), plotting within the three-phase zone, and display apparent CSIs of approximately 9 for females and 7 for males on this phase diagram. Note that a hypothetical line connecting control and transgenic bile extrapolates to the cholesterol apex of the triangle, a phenomenon not usually encountered in the murine lithogenic state (12). This implies that biliary phospholipid secretion was uncoupled from cholesterol secretion by ABCG5/ABCG8 overexpression, thereby limiting the molar ratio of cholesterol that could be solubilized by phospholipid at the canalicular level.