Twenty euthyroid patients with retarded depression were studied to determine the possible role of alterations in thyroid function in the etiology and treatment of depression. A battery of tests was administered regularly to measure change. Patients responded better to usual doses of imipramine when 25 µg. of L-triiodothyronine (T3) was administered daily. T3 was physiologically active, altering protein-bound iodine values and accelerating ankle reflex time. A possible explanation, based on relevant data from animal experiments, is that imipramine may elevate effective biogenic concentration, while T3 increases receptor sensitivity.