Six of 237 (2.5%) patients with chronic viral hepatitis who were treated with recombinant interferon alfa developed thyroid disease while on treatment. Three patients developed hyperthyroidism, two of whom developed detectable levels of thyroid-stimulating immunoglobulin; three patients developed hypothyroidism in association with high titers of antithyroglobulin and/or antimicrosomal antibodies. The thyroid disease did not remit when interferon therapy was stopped, and all six patients required definitive therapy for the thyroid disease. These findings suggest that a small proportion of patients treated with interferon alfa develop autoimmune reactions and can develop autoimmune thyroid disease.