The clearance of 5-hydroxyindoleacetic acid from the cerebrospinal fluid of cats was studied. Clearances were low during ventriculocisternal perfusions. The clearances were five times greater during spinal subarachnoid perfusions and 10 times greater during cortical subarachnoid perfusions. The cortical subarachnoid clearances can be resolved into a saturable mediated transport mechanism and a diffusional component. The mediated transport Component was blocked both in this system and in the spinal subarachnoid system by pretreatment with probenecid. A mechanism consistent with the above data is proposed for the clearance of cerebrospinal fluid monoamine metabolites from the central nervous system.