Abstract: A multidrug-resistant(mdr)clone of human cancer KB cells was isolated by step-wise selection on exposure to increasing doses of vincristine. The final clone ,KB_V200 ,obtained afterethylmethane sulfonate(EMS)mutagenesis showed 175-fold higher resistance to vincristine than didKB crlls. The cells were also cross-resistant to taxol, colchicine and adriamycin. Cellular accumlation of vincristine in KB_V200 was decreased to less than one-fifth of that in KB.To determine the presence of mdr 1 mRNA in KBV200 and KB ,total cellular RNAs from each cell linewere analyzed by means of slot blot hybridization The result showed that the mdr 1 gene had beenhighly expressed in KB_V200. In addition , verapamil,a calcium channel blockers ,was shown to increase VCR accumulation inKB_V200 and reverse the vincristine resistance. All these results demonstrate that the mechanism ofKB_V200 cell resistance to multiple drugs resulted from increased expression of mdr 1 gene and brought about over production of P-glycoprotein and increased the efflux of drugs.