In order to further define the role of the MDR1 gene in acute myeloid leukemia (AML), we determined the association between the presence of P-glycoprotein on leukemic cells and the efficacy of therapy in patients with AML. Immunocytochemistry with monoclonal antibody C219 was performed to demonstrate the presence of P-glycoprotein. Positive staining ranged from 0 to 60% of the leukemic cells. For further analysis, patients were assigned into groups with 0-5% staining cells (group 1, n = 33) and with > 5% staining cells (group 2, n = 19). The complete remission rate of induction chemotherapy was 76% for group 1 but only 32% for group 2 (p = 0.002). The median duration of overall survival was 19 months for patients in group 1 as compared to 3 months for patients in group 2 (p = 0.007). The data indicate that P-glycoprotein expression is associated with an unfavorable prognosis in patients with AML.