The thyroid hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of thyroid hormone. Generalized resistance to thyroid hormone (GRTH) is characterized by resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum thyroid hormone levels and normal or elevated TSH levels and are clinically thyrotoxic. Therapy is usually necessary, but current choices are not completely satisfactory. Selective peripheral resistance to thyroid hormone (PerRTH) is characterized by resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum thyroid hormone and TSH levels but was clinically hypothyroid and improved with thyroid hormone administration. All of these disorders are probably more common than is generally recognized and are often misdiagnosed and inappropriately treated. GRTH, in most cases studied, results from a mutation in the thyroid hormone receptor beta gene causing an amino acid substitution in or a partial or complete deletion of the thyroid hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined.