The physiological model developed focuses on the various rates controlling the transfer of 6MP between the CSF and systemic circulation. Analysis indicates that transfer of 6MP into CSF via cerebral capillaries when injected systemically or into systemic circulation when injected intraventriularly may be minimal e.g. less than 5%, thereby suggesting that primary route of drug entry into CSF in at choroid plexus in the newly formed CSF and primary route of drug exiting the CSF is via the arachnoid villi by bulk-flow of the CSF. Involvement of active carrier mediated transfer has not been completely ruled out. Analysis suggests new experimental approaches and dosing stratagies for treatment of meningeal leukemia.