In recent years recombinant alpha-interferons (alpha-IFNs) have been widely used in the treatment of several hematological malignancies. Prolonged courses of IFN have been shown to induce autoantibodies and to support the exacerbation or even the development of autoimmune diseases. In this report we describe the development of symptomatic autoimmune thyroid diseases in 4 (7.4%) out of 54 patients in chronic treatment with recombinant alpha-IFNs in our department. Two patients developed a disease resembling Hashimoto's thyroiditis after 17 and 49 months of continuous IFN treatment, while the other two developed a typical Graves' disease after 41 and 52 months of therapy. The mechanism by which IFN induces autoimmune thyroid diseases, the choice of searching for anti-thyroid autoantibodies before starting long-term IFN treatment, the option of discontinuing IFN therapy in the presence of overt thyroid diseases, and the management of these diseases are discussed.