In recent years recombinant alpha interferon (IFN) has been widely used in the treatment of neoplastic and infectious diseases. Induced autoimmune disorders and thyroid impairment are getting increasing relevance in the field of side-effects complicating long-term alpha-interferon courses. We monitored thyroid function in 35 patients receiving alpha-IFN therapy for different diseases (chronic hepatitis, essential thrombocytemia, multiple myeloma, chronic myeloid leukemia, essential polycytemia, essential crioglobulinemia and hairy-cell leukemia). All of them were euthyroid and negative for anti-thyroid serum antibodies before treatment. Six months later, 6 patients (17%) developed primary hypothyroidism with elevated antithyroid antibodies in 5 cases; 1 continuing to be negative. None of our patients developed hyperthyroidism. Overall, "indirect-autoimmune" and "direct non autoimmune" mechanisms are considered possible and/or combined pathogenetic moments of thyroid disfunction during alpha-IFN therapy. Thyroid complications mainly occur when latent impairment of immune system exists. Thyroid circulating hormones levels and autoimmunity screening should be performed in all patients before starting and during long-term alpha-IFN treatment.