Thyroid dysfunction developed in 35 patients among a series of 300 (190 men and 110 women) treated with alpha-interferon (35/300 = 12%. No relationship was observed between the type of alpha-interferon, the dose, or hepatic response, but there were more women (24/35). Antithyroid antibody levels were frequently elevated before treatment (8/35, 23%). Hypothyroidism developed in 27 patients, 7 with clinical hypothyroidism, 10 with moderate hypothyroidism and 5 with elevated TSH only. Patients with severe symptoms and highly elevated thyroid antibodies were more prone to develop sustained or irreversible hypothyroidism (10 patients). Twelve patients recovered a normal thyroid function within a few months, but antibody levels fell more slowly. Primary hyperthyroidism of variable severity appeared in 13 patients. In 8 patients, normal thyroid function was recovered within a few weeks but thyroid antibodies remained high for at least one year. In 5 others spontaneous hypothyroidism occurred within a few weeks ("biphasic" hypothyroidism). Direct toxicity appears to be less probable than an autoimmune mechanism; elevated antithyroid antibodies were observed in only 20 patients (57%). In clinical practice, TSH levels should be regularly monitored during and after alpha-interferon therapy.