OBJECTIVE: Computerized tomography(CT) and magnetic resonance imaging(MRI) are very useful in detection of structural change in the brain including tumors. However, they can not inform functional and biological behavior of such lesions. 99m Tc-Methoxyisobutyl isonitrile(MIBI) is considered as a substrate for MDR1 gene-encoded permeability glycoprotein(P-gp) and it has been used in the evaluation of multidrug resistance(MDR) in various tumors. The purpose of the study is to demonstrate the presence of MDR in brain tumor and brain tumor grading by an external imaging with 201Thallium and 99m Tc-MIBI SPECT. METHODS: 201Thallium and 99m Tc-MIBI SPECT were performed in 18 patients with malignant tumors and in six patients with benign tumors. Immunohistochemical staining(IHC) of the tumor specimen for P-gp was also performed. The histologic grading of the tumors and immunohistochemical staining for P-gp were compared to the dual brain SPECT findings of 201Thallium and 99m Tc-MIBI SPECT studies. Brain tumor with positive 201Thallium SPECT and negative 99m Tc-MIBI SPECT is considered to be multidrug resistance. An uptake index obtained from brain SPECT was used for tumor grading. MDR1 gene-encoded P-gp was assessed by immunohistochemical staining using a monoclonal antibody for P-gp. RESULTS: The malignant group showed significantly higher uptake indices in the 201Thallium and 99m Tc-MIBI SPECT than benign group. The uptake index of 99m Tc-MIBI SPECT was inversely correlated with P-gp immunohistochemical staining without statistical significance. CONCLUSION: 201Thallium and 99m Tc-MIBI SPECT are useful for predicting histologic grade of brain tumors, and 99m Tc-MIBI SPECT might be useful for predicting the presence of MDR protein.