We examined the ability of partially synthesized new compounds from fangchinoline and tetrandrine to reverseP-glycoprotein (P-gp)-dependent multidrug resistance (MDR) in vitro and in vivo. All compound enhancedthe in vitro cyctotoxic effect of vinblastin (VBL) at 0.1mM as potent as 10mM verapamil against the resistant cellline P388/ADR. The combination effect tended to be strong by substitution of bulky group, resulting 5,14-dibromotetrandrine(compound #9) showed the strongest effect. Compound #9 increased intracellular VBL accumulationin P388/ADR cells, much stronger than verapamil, as well as cytotoxic combined effect. This mechanismseems to inhibit the function of P-gp, but not the expression of P-gp. In combination with VBL, this compoundalso synergistically prolonged the life-span of P388/ADR-bearing mice. Bisbenzylisoquinoline alkaloids and theirderivatives are possible to be good candidates as modifier of MDR in cancer chemotherapy.