The administration of sulfobromophthalein sodium (BSP) to manganese-loaded animals had been found to prevent effectively the cholestasis normally created by bilirubin infusion following manganese loading. Measurement of bilirubin levels in blood, liver, and bile in manganese-bilirubin animals with and without BSP fails to provide convincing evidence for a BSP-induced shift in site or magnitude of total bilirubin concentration as an explanation for this anticholestatic action of BSP. Nevertheless, increasing the dose of bilirubin partially reinstitutes the cholestasis. The results are important in that they demonstrate (1) that under certain circumstances intrahepatic cholestasis can be immediately and directly prevented by a pharmacologic agent (by a means not as yet defined) and (2) that the cholestatic activity of bilirubin is, to some extent or under some circumstances, separable from its concentration in blood, liver, and bile.