Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long‐term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha‐interferon (IFN) exerts a dose‐dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non‐mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha‐IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1–3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9–12 months). Also patients resistant to cytotoxic drugs may respond to alpha‐IFN, suggesting a lack of cross‐resistance between the two treatment modalities. Side‐effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low‐dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha‐IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.