In 10 hyperthyroid women studied in the follicular phase of the menstrual cycle, basal plasma PRL was normal, but PRL release after TRH was significantly suppressed compared with that in 11 control women. The suppressed PRL response to TRH was not explained by changes in serum estradiol or sex hormone-binding globulin. It recovered after treatment of hyperthyroidism. When normal women were treated with T4 (0.5 mg daily for 6 to 10 days), their mean serum free T4 level increased to about 70% of that in the hyperthyroid patients, whereas their serum free T3 levels increased to a lesser degree. During T4 administration, these women had PRL changes similar to those of the hyperthyroid patients. When the normal women took T3 (60-120 micrograms for 6 to 8 days), their serum free T3 increased to almost the level of the hyperthyroid patients, but the TRH stimulated PRL release remained close to the control level. The PRL increase after dopaminergic blockade with metoclopramide was significantly suppressed in hyperthyroid patients, and they had no PRL response to TRH after pretreatment with metoclopramide. In conclusion, the PRL changes in hyperthyroidism were reproduced by administration of T4, but not by administration of T3 to healthy women. The site of action is suggested to be pituitary, but additional hypothalamic effects cannot be excluded.