The administration of phenobarbital to rats enhanced hepatic uptake of an organic anion, bromsulphalein, in vivo and simultaneously increased the amount of Y, a hepatic cytoplasmic organic anion-binding protein. This study supports the postulate that Y is a major determinant in the selective hepatic uptake of certain organic anions from plasma. Induction of Y may contribute to the enhanced hepatic uptake and metabolism of various organic anions (drugs, hormones, etc.) produced by phenobarbital and other agents.