Previous experiments suggest the primary route of valproic acid (VPA) removal from the rabbit central nervous system (CNS) is by probenecid-sensitive transporters at the blood-brain barrier but not at the choroid plexus. The purpose of this study was to determine if other transport mechanisms at the choroid plexus played a significant role in the removal of VPA from the CNS. In six rabbits, silicone oil was perfused into both cerebral ventricles and out through the cisterna magna to physically block exchange of VPA between cerebrospinal fluid (CSF) and blood and between brain and CSF. In six control rabbits, perfusion was performed with mock CSF. Both groups received a loading dose followed by continuous intravenous infusion of VPA for 210 min. Ventriculocisternal perfusion with silicone oil had no significant effect on the steady-state brain concentrations or brain-to-plasma concentration ratios of VPA, further confirming that efflux of VPA at the choroid plexus is negligible.