In this article, stress is used simplistically as a general term for pathophysiological conditions associated with a stimulation of the hypothalamus-pituitary-adrenal (HPA) axis that are not caused by pathological abnormalities in the HPA axis itself. These stress conditions include those inflicted by disease, inflammation, injury, surgical trauma, fasting, heat and cold exposure, and emotional stress. In addition to stimulating of the HPA axis, these conditions are often associated with profound alterations in several thyroid-related parameters, which are commonly referred to as the low T 3 syndrome. Stress-induced alterations in thyroid hormone bioactivity result to an important extent from the centrally mediated suppression of thyroid function and the inhibition of the peripheral conversion of the prohormone thyroxine (T 4) to the active hormone triiodothyronine (T 3). Both central and peripheral effects may be mediated in part by the high cortisol levels. This article first gives a brief introduction to the regulation of thyroid hormone levels and bioactivity. Subsequently, it describes in some detail the stress-induced changes in thyroid hormone regulation at the central and peripheral levels and speculates about the role of increased cortisol levels in these changes.