These experiments demonstrate that the cholestasis following manganese-bilirubin administration varies directly in severity in relation to the amount of bilirubin administered. This suggests that the cholestasis is related to critical bilirubin accumulation in some compartment of the biliary excretory pathway. However, in the immediate precholestatic period, the levels of bilirubin in all three compartments of blood, liver and bile also vary in direct relation to the amount of bilirubin administered. The critical site of bilirubin accumulation or concentration is not, therefore, defined by these experiments.