In order to evaluate the effects of severe trauma on the levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (reverse-T3, r-T3), blood samples were collected from traumatized patients on the first post-trauma day. The plasma concentrations of T3 were significantly decreased (mean, 47.4 ng/dl); T4 levels were in the normal range (mean, 6.6 mcg/dl) and r-T3 levels were significantly elevated (mean, 80.8 ng/dl). The oxygen extraction by the muscular tissue was also determined in these patients and found to be elevated; however, no correlation could be established between the extraction ratios and the thyroid hormone levels. This deviation in the peripheral conversion of T4 into r-T3 with a decreased production of T3 also accompanies severe systemic illnesses and probably represents a form of T4 inactivation conditioned by the metabolic demands of the body. This alternate pathway of thyroid hormone metabolism is enhanced by elevated blood levels of catecholamines, glucose, or glucocorticoids as well as by decreased insulin plasma concentrations, all known to follow major trauma and other catabolic conditions.