An increasing number of disorders that may cause hyperthyroxinemia without thyrotoxicosis have been recognized in recent years. These include acquired and inherited abnormalities of serum thyroid-hormone-binding proteins, peripheral resistance to thyroid hormones, acute nonthyroidal illness, acute psychiatric illness, and some drug-induced conditions associated with nonthyrotoxic elevations of serum thyroxine. In addition to the laboratory finding of elevated serum thyroxine levels, many of these syndromes are also accompanied by abnormalities in triiodothyronine and free thyroid hormone levels, as well as unresponsiveness of thyroid-stimulating hormone to thyrotropin-releasing hormone, all of which further erroneously indicate a diagnosis of thyrotoxicosis. An awareness of these syndromes and alterations in the results of thyroid function tests that accompany them is important to prevent a misdiagnosis of hyperthyroidism and inappropriate therapy.