Previous studies have shown that acute nonlymphocytic leukemias are clonal diseases in which there is heterogeneity in the pattern of stem cell differentiative expression. To determine whether M7 megakaryocytic leukemia is a clonal disease and to evaluate the differentiative expression of the cells involved by the leukemia we studied a patient with megakaryocytic leukemia who was heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). The diagnosis of megakaryocytic leukemia was based on results obtained with the immunogold method and ultrastructural studies with the monoclonal anti-Gplla/IIIb antibody, 10E5. Direct testing of blood and marrow mononuclear cells and blood platelets demonstrated only A-type G6PD, whereas skin exhibited both B and A enzymes. The results indicate that the megakaryocytic leukemia in this patient was clonal at the time of study. To determine the differentiative expression of the stem cells, granulocyte/macrophage colony forming units and erythroid burst forming units were cultured and the resultant colonies were tested for G6PD. The results indicate that the stem cells involved by the leukemia exhibited differentiative expression multipotent for the megakaryocytic and granulocytic pathways, but no definitive conclusion could be made regarding the erythroid lineage.