The c-sis gene expression in leukemia cells from a patient with acute megakaryoblastic leukemia and Down's syndrome was studied. The leukemia blasts were identified as megakaryoblasts by the platelet peroxidase reaction and the reactivity against antiplatelet monoclonal antibodies. Leukemia cells obtained from peripheral blood or bone marrow specimens before and after initiation of chemotherapy were analyzed for c-sis gene expression by the RNA-DNA dot blot hybridization. Although the level varied, the mRNA of the c-sis gene was detected in all megakaryoblastic leukemia cells obtained at different clinical stages. The c-sis mRNA level in cells obtained after relapse was higher than that obtained before the initiation of therapy. The 25S c-sis mRNA was detected in a megakaryoblastic leukemia cell line established from this patient. The role of the expression of the c-sis gene in acute megakaryoblastic leukemia cells is discussed.