To determine an index of adequate suppression of pituitary TSH secretion in euthyroid goitrous patients treated with sodium levothyroxine (T4), TSH responses to 500 micrograms TRH given iv were compared with thyroid 24-h radioiodine uptakes during therapy with T4 in 12 euthyroid goitrous patients. The patients received sequentially 100, 150, 200, 250, and 300 micrograms T4 with the doses increased at 4-6 week intervals. The mean dose of T4 that reduced the peak TSH response to TSH to the lower limit of normal (TSH = 5 microU/ml) was 130 micrograms; the mean T4 dose that suppressed the TSH response to one-half the lower limit of normal (TSH = 2.5 microU/ml) was 165 micrograms. The mean T4 dose that nearly obliterated the TSH response was 200 micrograms; this degree of suppression occurred with doses of 100-300 micrograms T4 in individual patients. Suppression of thyroid uptake correlated closely with suppression of the TSH response to TRH. The goiter diminished in size significantly in 6 of the 12 patients during the 6 months of observation adn did not enlarge in any patient. The data indicate that suppression of the TSH response to TRH is a convenient technique to assess the adequacy of suppressive therapy of goiter.