To evaluate the frequency and the prognostic value of different mechanisms of drug resistance in acute leukemias, we investigated the expression of mdr1 by immunocytochemistry, mRNA slot blot or RT-PCR in 182 cases of adult acute myeloid and 37 cases of adult lymphoblastic leukemia. Before treatment, 39% of de novo AML, 38% of secondary AML, and 7% of de novo ALL exhibited a high level of mdr1 mRNA. After chemotherapy, the frequency of mdr1 gene expression in ALL raised dramatically to 60% (P < 0.005), while no significant change was found for AML cases. In 91 patients treated with MDR-related drugs, mdr1 gene expression was related to the failure of chemotherapy (P < 0.0001). The overexpression of multidrug resistance-associated protein (mrp) and anionic glutathione S-transferase (GST pi) was also investigated in 38 and 61 AML patients respectively. An overexpression of mrp gene was noted in 39% of the cases. For GST pi gene, the frequency of overexpression was 28%. A positive and significative correlation was found among mdr1, mrp and GST pi genes expression.