Recently, we and others could define the molecular cause of the rare disease congenital amegakaryocytic thrombocytopenia (CAMT) as mutations in the c-mpl gene (Blood 97: 139, 2001). We proposed that c-mpl mutations are the cause not only for the hypomegakaryocytic thrombocytopenia, but also for the development of an aplastic anemia (AA) in patients with CAMT. The effects of thrombopoietin (TPO) on early multipotent hematopoietic progenitors were elucidated by a recent series of in vitro and in vivo studies. Like CAMT patients, mice lacking the TPO receptor c-Mpl demonstrate a major reduction of early hematopoietic progenitor cells of all lineages. However, these mice achieve a normal marrow cellularity and composition, despite the lack of megakaryocytes. On the other hand, the incidence of development of aplastic anemia in CAMT is not clear owing to difficult and not consistent diagnosis of this disease.