GENERALLY, the purpose of assessing thyroid function in a given patient is to determine his metabolic status. In patients with systemic nonthyroidal illness, as well as in those undergoing a variety of other stresses, this determination is complicated by effects at all levels of the hypothalamic-pituitary-thyroid axis. With the availability of thyrptropin releasing hormone (TRH) and the recent development of sensitive methods for the direct measurement of serum 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3 (rT3)), considerable progress has been made in gaining an understanding of the significance of the alterations in thyroid hormone economy that accompany nonthyroidal illness, stress, and the administration of certain pharmacological agents. According to basic tenets of negative feedback control of thyrotropin (TSH) secretion by circulating free thyroid hormones, alterations in hormone binding in nonthyroidal illness that produce increases in free hormone should result in predictably decreased TSH responses to TRH stimulation. Indeed, the magnitude of TSH response to TRH is often taken to be the most specific clue to the true metabolic state of the organism, and the recent publication of studies that examined the status of TRH responsiveness in nonthyroidal illness has provided critical information in this regard.