Severe congenital neutropenia (SCN) or Kostmann's syndrome is a congenital disorder characterized by persistent, severe, absolute neutropenia, usually detected within the first months of life and associated with a maturation arrest of neutrophil precursors at the myelocytic stage. Transformation of SCN into acute nonlymphoblastic leukemia with and without treatment with G-CSF has been reported. Recently point mutations in the gene of the G-CSF receptor were identified in some patients with SCN. We present a boy with a history of recurrent infections since birth. The diagnosis of SCN was confirmed at the age of 3 months based on clinical manifestations, persistent severe neutropenia, and profound deficiency of granulocyte precursors with maturation arrest at the myelocytic stage in the bone marrow(BM). Cytogenetic study of BM cells was normal (46XY) while in vitro cultures of BM cells showed a normal number of myeloid (CFU-GM) and erythroid (BFU-E) colonies. Morphologic examination of these colonies revealed immature granulocyte precursors, only. Initially the patient was treated with various antibiotics but due to recurrent severe infections, G-CSF was administered subsequently on a daily schedule, leading to profound clinical and hematological improvement. At the age of 7 ½ years, 52 months after G-CSF treatment,the patient presented with hepatosplenomegaly, urticaria rash, diabetes insipidus and progres-sively severe anemia. Myeloblasts (8%) appeared in the peripheral blood, while the BM examination revealed dyserythropoiesis and blasts > 10% (MDS-RAEB-t). Cytogenetic analysis showed monosomy 7. A progressive clinical and hematologic deterioration followed and 6 months later a full blown AML was developed (CD33:73%, CD13:97%, CD14:19%, HLA-DR:57%). G-CSF administration in patients with SCN is undoubtfully useful in the quantitative and functional restoration of the myeloid line. The frequency of severe infections is reduced and the quality of life is improved. Recently, however, there has been some debate on the possible mechanisms by which long-term administration of G-CSF could initiate an hematologic malignancy, in patients with potentially preleukemic situations such as Kostmann's syndrome. It is argued that G-CSF can either increase the survival of Kostmann's syndrome allowing evolution of the disease to leukemia, or act as a cofactor in an already disbalanced cellular function.