Taken together, these findings demonstrate that: 1) MDR is often an insurmountable impediment to cancer chemotherapy; 2) In the case of brain tumors, MDR1 acts by a dual mechanism: a pharmacokinetic one mediated by endothelial cells at the blood-brain barrier and a pharmacodynamic one at the tumor cell plasma membrane where multidrug resistant transporters are widely expressed. The gene discussed is ABCB1; the disease is neoplasm.