Generalized resistance to thyroid hormone is a rare condition; affected individuals have elevated serum levels of free thyroxine and free triiodothyronine with inappropriately normal or slightly elevated levels of thyrotropin, yet are generally clinically euthyroid. However, responsiveness to thyroid hormone varies from tissue to tissue, and some patients may benefit from treatment with exogenous hormone. We have described the case of a patient with this disorder who initially had a mildly elevated serum thyrotropin level and was clinically euthyroid but in whom symptomatic autoimmune hypothyroidism subsequently developed. The serum free thyroxine level, although diminished from its previously elevated value, remained within the normal range. The patient required substantial doses of levothyroxine to return basal and stimulated TSH to their prior levels. Criteria for the treatment of adults with this disorder have not been firmly established. This case suggests that one indication for thyroid hormone supplementation may be the presence of high-titer serum antithyroid antibodies in patients who initially have mildly elevated thyrotropin values; they could be at increased risk for progression to overt hypothyroidism.