2 patients with chronic viral hepatitis were treated with alpha-interferon and developed thyroid dysfunction. Both patients were previously euthyroid and had thyroids of normal size. 1 developed hypothyroidism (FT4 0.49 micrograms/dl; TSH 26.8 mIU/ml) and the other developed hyperthyroidism (FT4 2.72 micrograms/dl; T3 366 ng/ml; TSH 0.15 mIU/ml) 4 and 6 months, respectively, after commencing interferon. Interferon was discontinued, and thyroid function tests returned to normal within 1 and 2 months, respectively, and have remained normal for over a year. Antimicrosomal antibodies in the hypothyroid patient were positive (1:6400), but became negative after 4 months. No specific therapy for the thyroid disorders was given. These findings suggest that alpha-interferon induced transient thyroid dysfunction in patients who were previously euthyroid and were negative for thyroid autoantibodies.