Alterations in thyroid physiology and thyroid function tests occur in some patients with nonthyroidal illnesses. Low concentrations of serum triiodothyronine (T3) usually occur in nonthyroidal illnesses and are attributable largely to reduced extrathyroidal conversion of thyroxine (T4) to T3. Concentrations of serum total T4 may be low, normal, or high; alterations in serum binding of T4 explain the abnormality in most cases. Concentrations of serum reverse T3 are usually high because metabolic clearance is reduced. Whether patients with nonthyroidal illnesses with low T4 or T3, or both, are hypothyroid is uncertain; concentrations of free T4 have been estimated as low, normal, or high using different methods. Serum thyroid-stimulating hormone is typically normal. Low concentrations of T3 or T4, or both, in nonthyroidal illnesses may have a homeostatic significance. Low serum concentrations of T4 correlate with poor prognosis in nonthyroidal illnesses. Inhibitors of thyroid hormone binding and phagocytosis are present in normal tissues. Leakage of the inhibitors into the circulation may lower serum concentrations of T4 on one hand and compromise critical host defenses on the other.