The acute effect of triiodothyronine (T3) on mobilization of fat and protein energy stores has been measured in five fasting, normal men. Fasting subjects were chosen for this study to amplify catabolic effects occurring during brief thyroid hormone treatment. Subjects were fasted for 72 hr on two occasions with admintration of T3, 150 mug every 12 hr, for 72 hr before and during the second fast. Plasma beta hydroxybutyrate, acetoacetate, and free fatty acid levels as well as ketone, creatine, and urea excretion were measured during control and T3 fasts. T3 enhances catabolism of protein stores as indicated by the doubling of urea excretion during the T3 fasts. Likewise, creatine excretion is increased six to ninefold during the T3 fasts. Catabolism of fat stores is enhanced during the T3 fasts as shown by increased plasma free fatty acid and ketone levels, and increased ketone excretion. Brief T3 treatment for 3 days augments the expected protein and fat catabolism of starvation without causing subjective changes of hyperthyroidism. Much of the catabolic expression of hyperthyroidism may simply reflect inadequate caloric intake to fuel energy requiring processes stimulated by thyroid hormone such as cell membrane sodium pumping and protein synthesis.