In nine euthyroid goitrous patients, increasing doses of T4 caused a significant decrease in the PRL response to TRH; the PRL response fell significantly at a dose of T4 of 100 micrograms/day for 1 month (P less than 0.02) and fell further with increasing doses so that at 300 micrograms T4/day, the PRL response was 40% of that in the untreated state. T4 treatment also blunted the PRL response to chlorpromazine (P less than 0.05) in a separate group of euthyroid goitrous patients. In contrast, there was only a small drop of the PRL response to TRH in normal subjects treated with T4 (n = 9) and none at all with T3 (n = 7). These data, together with previously published reports, suggest that thyroid hormone may affect PRL secretion in the presence of thyroid disease (hyperthyroidism, hypothyroidism, or euthyroid goiter), but that physiological amounts of thyroid hormone have little or no modulating effect on PRL secretion in normal persons.