BACKGROUND: The development of antibodies to thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone (TSH) receptor is a main feature of autoimmune thyroid diseases. OBJECTIVE: To investigate whether complete removal of thyroid antigens results in the abatement of humoral thyroid autoimmunity. DESIGN: Retrospective chart review study of patients treated and monitored with a standard prospective protocol. SETTING: University hospital in Pisa, Italy, between 1976 and 1994. PATIENTS: 182 patients with differentiated thyroid carcinoma and serum antibodies to thyroid peroxidase, thyroglobulin, or TSH receptor due to coexistent clinical Hashimoto thyroiditis, Graves disease, or focal autoimmune thyroiditis. INTERVENTION: Total thyroidectomy and radioiodine treatment to ablate residual or metastatic thyroid tissue. Regular follow-up with iodine-131 whole-body scanning and serum thyroglobulin measurement. Mean follow-up (+/-SD) was 10.1 +/- 4.1 years (range, 4 to 20 years). MEASUREMENTS: Serum antibodies to thyroid peroxidase, thyroglobulin, and TSH receptor. RESULTS: Thyroid peroxidase, thyroglobulin, and TSH-receptor antibodies progressively disappeared after the initial treatment. The median disappearance time was 6.3 years for thyroid peroxidase antibodies and 3.0 years for thyroglobulin antibodies. There was a statistically significant correlation between the disappearance of thyroid tissue and that of thyroid antibodies. The coexistence of Hashimoto thyroiditis or Graves disease with thyroid cancer did not modify the pattern of disappearance of thyroid antibody compared with patients with focal autoimmune thyroiditis. CONCLUSIONS: Complete ablation of thyroid tissue with its antigenic components results in the disappearance of antibodies to all major thyroid antigens, thus supporting the concept that continued antibody production depends on the persistence of autoantigen in the body.