1. Ventriculo-cisternal perfusions were performed on rabbits with artificial cerebrospinal fluid containing blue dextran and tritium-labelled prostaglandin F(2alpha) ([(3)H]PGF(2alpha)). In order to study the nature of prostaglandin (PG) transfer across the blood-brain barrier, high concentrations of PGF(2alpha) or potential PG transport inhibitors were added to the perfusion fluid after the normal rate of [(3)H]PGF(2alpha) clearance was established.2. The [(3)H]PGF(2alpha) clearance was inhibited by 10(-6) to 10(-3)M PGF(2alpha), PGF(2beta), probenecid, iodipamide or bromcresol green but not by perchlorate.3. The (3)H content of the brain, relative to the (3)H-activity in the ventricular system, was also increased by high concentrations of PGF(2alpha), iodipamide or bromcresol green.4. It is concluded that the removal of PGs from the extracellular fluids of the brain is mediated by saturable, facilitated transport processes across both the choroidal and extrachoroidal regions of the blood-brain barrier system. In the case of the mammalian brain, such facilitated PG transport appears to be the primary mechanism for the termination of the action of these potent, endogenously produced autacoids.