To determine the pituitary-thyroid dysfunction in the manic patients receiving lithium carbonate, determination of thyroxine concentration, T3 Resin Uptake, thyrotropin concentration in plasma, and thyrotropin responses to administration of TRH, 500 mug i.v., were made. Eight manic patients were examined before and after lithium treatment, 600-1,200 mg daily, for four weeks. Slight reduction in the plasma levels of thyroxine, and slight increase in the plasma thyrotropin levels were seen following lithium treatment. Significantly enhanced thyrotropin responses to TRH administration were found as compared to the results before lithium treatment. It is assumed that lithium salts decrease both output of thyroid hormones and the sensitivity of the thyroid gland to thyrotropin, and that this action of lithium inhibiting the thyroid gland might be related to its anti-manic effect.