Expression of P-glycoprotein (P-gp), the multidrug resistance gene product, has previously been shown to be downregulated during differentiation of normal haematopoietic cells. In order to determine whether such a regulation also occurs in leukemic cells, we have investigated the relevance of differentiation levels to P-gp expression in multidrug-resistant leukemia K562R/7 cells and in parental drug-sensitive K562 cells. These leukemic cells were exposed to hemin and sodium butyrate, two known inducers of erythroid differentiation. Analysis of hemoglobin-synthesizing cells indicated that hemin induced both K562R/7 and K562 cells to differentiate into erythroid cells while sodium butyrate led to hemoglobin synthesis in only K562 cells. Northern blotting and immunolabelling experiments revealed elevated levels of MDR1 mRNAs and P-gp in both untreated and hemin-treated K562R/7 cells while P-gp expression was not detected in both uninduced and hemin-induced K562 cells. Flow cytometric analysis of cellular doxorubicin retention demonstrated that K562R/7 cells poorly accumulated the anticancer drug regarless their level of differentiation. These results therefore suggest that erythroid differentiation of leukemic drug-resistant K562R/7 cells in response to hemin treatment did not result in major alteration of P-gp expression and activity.