Marked alterations in levels of circulating thyroid hormone were found in patients undergoing cardiopulmonary bypass with a rise in the free thyroxine and a fall in the free triiodothyronine levels. Studies using thyrotropin-releasing hormone during bypass demonstrated a blunted response to this stimulus. This reduced response is related to changes in thyroid hormone levels and it is suggested that bypass surgery may have a direct inhibitory action on thyroid-stimulating hormone release at the hypothalamo-pituitary level. The potential significance of these hormonal changes is discussed.