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During a period of 7 years at our institution, four girls and one boy with Down's syndrome, ages 9 to 16 years, were examined and treated for hyperthyroidism. Two patients had Graves' disease and they responded to propylthiouracil (PTU) with a predictable clinical course resulting in remission within 4 years. The remaining three patients included in this report had hyperthyroid profiles similar to those of the two with Graves' disease except for their antibody panels. These patients, in addition to the elevated thyroid-stimulating immunoglobulin (TSI) level observed in Graves' disease, also had significantly elevated antimicrosomal antibody (AMA) and antithyroglobulin antibody (ATGA) at the time of diagnosis. Elevated TSI level was again present in two patients who had a recurrence of hyperthyroidism after PTU therapy was discontinued. Treatment of these three patients was best done with the continuation of PTU therapy at a lower dose and the addition of thyroxine as soon as mild hypothyroidism developed. Treatment with PTU and thyroxine was continued until the TSI level was no longer elevated. Levels of AMA and ATGA remained elevated long after the TSI level became normal. All three patients eventually had hypothyroidism and continue to require thyroxine replacement.