The multidrug-resistance phenotype in human tumors is partly associated with over-expression of the 170 kDa-P-glycoprotein encoded by the multidrug-resistance-1 (MDR1) gene. Another related, but non-P-glycoprotein, multidrug-resistance-associated protein (MRP) gene encodes a 190 kDa-membrane ATP-binding protein. Glioblastoma multiforme is a highly malignant primary neoplasm of the central nervous system which is refractory to anti-cancer chemotherapy, but the mechanism underlying this drug resistance is unknown. Out of glioma cell lines, 2, namely IN500 and T98G, which had elevated MRP mRNA levels, showed the highest resistance to multiple anti-cancer agents such as etoposide, vincristine and adriamycin, and decreased intracellular accumulation of etoposide. In the remaining 5 cell lines, various degrees of sensitivity to adriamycin and etoposide appeared to correlate with their respective MRP mRNA levels. Our study proposes that MRP may be involved in spontaneous multidrug resistance in human gliomas.