OBJECTIVE Treatment with recombinant interferon‐α (rIFN‐α) may induce autoimmunity. We have evaluated the effect of rIFN‐α on pre‐existing thyroid disease with special reference to changes in TSH receptor antibody.DESIGN AND PATIENTS Five patients, who had a history of autoimmune thyroid disease diagnosed between 2 and 16 years earlier (three patients had Graves' disease while two had Hashimoto's thyroiditis), were treated with rIFN‐α for chronic hepatitis C. Before, during and after rIFN‐α therapy, we determined thyroid function, antithyroid antibody, thyroid echogenicity and the surface phenotype of the peripheral and intrathyroidal lymphocytes.RESULTS Four of the patients developed overt hypothyroidism after 4–7 months of rIFN‐α therapy, and two of them had a preceding history of low‐uptake thyrotoxicosis. Recovery of thyroid function was observed in all four patients. Strongly positive blocking type TSH receptor antibody was detected and an increase in the percentage of CD19 positive cells in the intrathyroidal lymphocytes was also observed in three of the patients even though the goitre size increased in two of them. One of the patients became thyrotoxic later when stimulating type TSH receptor antibody became positive. Another patient suffered from reversible hypothyroidism although stimulating type TSH receptor antibody remained strongly positive throughout the clinical course.CONCLUSIONS Our data thus indicated a high incidence of an unusual type of reversible hypothyroidism with TSH receptor antibodies in patients with chronic hepatitis C and pre‐existing autoimmune thyroid disease after recombinant interferon‐α therapy through a mechanism involving both the