Treatment of essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with myeloid metaplasia (MMM) patients is frequently a difficult issue. To date, there is no generally accepted treatment for these diseases which can reduce the risk of thromboembolism and/or haemorrhagic events, avoid any increase in the frequency of secondary myelofibrosis and terminal blast transformation and decrease the reticulin content in the bone marrow of MMM patients. The most frequently used myelosuppressive agent is hydroxyurea (HU), but widespread application has failed to demonstrate that is not leukaemogenic. In patients with MMM, conflicting results have been obtained following alpha-IFN treatment. Haematological responses have been seen in 50% of the patients. Usually the patients showing good responses had a hyperproliferative type of disease. In only one case was a reduction of reticulin content of the bone marrow observed. Thus, these findings do not indicate alpha-IFN as a first-line therapy. On the other hand, the results of several reports in ET and PV patients have shown a reduction in the abnormal proliferation of megakaryocytes and erythroid elements, following alpha-IFN treatment. A reduction in spleen size has also frequently been seen. Together with the improvement of haematological parameters, clinical symptoms have also responded positively. Long term control of these diseases can be obtained with a well-tolerated low dose of alpha-IFN. However, PV and ET are not usually characterized by cytogenetic abnormalities, making it very difficult to demonstrate the disappearance of clonal haemopoiesis following alpha-IFN therapy, even if this does occasionally occur, as evident from the two cytogenetic convertions described in the literature. As compared to myelosuppressive drugs or phlebotomy, alpha-IFN thus represents an attractive new treatment, able to exert a fundamental influence on these diseases, presumably without any untoward leukaemogenic or gonadotoxic activity.