The response of PRL to the oral administration of the dopamine receptor-blocking agent metoclopramide and the effect of metoclopramide on the TRH-induced release of PRL and TSH were measured in eight patients with hyperthyroidism and in eight age- and sex-matched euthyroid controls. As expected from the known direct inhibitory influence of thyroid hormones on pituitary TSH secretion, there was no TSH rise in response to metoclopramide in either group. PRL levels, on the other hand, rose significantly after the administration of metoclopramide in both the hyperthyroid and euthyroid subjects (P less than 0.0005 at 60 and 120 min). However, the increase in PRL at 120 min was significantly less in the hyperthyroid subjects than in the euthyroid controls (P less than 0.0025). Furthermore, the administration of metoclopramide failed to reestablish normal responsiveness of either PRL or TSH to TRH in the hyperthyroid subjects. We have previously suggested that thyroid hormones inhibit PRL secretion by stimulating the hypothalamic secretion of dopamine. These results suggest, however, that elevated levels of thyroid hormones also inhibit PRL release directly at the anterior pituitary level.