Systemic mastocytosis (SM) are defined by an abnormal growth and accumulation of mast cells in bone marrow and/or other extracutaneous organs. There is currently no cure for this disease. Because of similarities and/or association of mastocytosis with myeloproliferative disorders, interferon alpha has been tested but with contradictory reported results. A first prospective multicenter phase II trial was then started in France. From 1994 to 1997, 20 adult patients with confirmed bone marrow involvement received interferon alpha-2b for at least 6 months, (from 1 million U per day up to 5 million U/m(2)/day). Thirteen patients who presented systemic and/or specific cutaneous manifestations, demonstrated objective responses: seven (35%) were partial, six (30%) minor but no complete response could be observed at the time of analysis. The bone marrow remained unchanged in 12/13. Thus, interferon should be offered to patients with severe systemic manifestations, who have not responded to symptomatic therapies, even in case of non-aggressive mastocytosis, with or without corticosteroids the first weeks. Long-term therapy should be offered to patients with initial positive response. To control more aggressive SM or mastocytosis associated with clonal hematologic non-mast cell lineage or leukaemia mast cell, other chemotherapeutic regimens should be proposed like Cladribine (2-chlorodeoxyadenosine, 2-CDA) or polychemotherapies including interferon as it is being tested in France in a new multicentric protocol, coordinated by the association AFIRMM, with interferon and oral cytarabine.