A study of the effect of alpha-methyl-1-tryosine (metyrosine) blockade (2 g/d for 2 d) of dopamine (DA) synthesis on the PRL and TSH response to domperidone (DOM) and TRH in normal women and subjects with pathological hyperprolactinaemia is reported. In the normal subjects, there was a marked increase in basal PRL (51.7 +/- 11.1 vs 5.7 +/- 1.0 ng/ml) and the PRL and TSH responses to DOM were abolished. The PRL response to TRH was also reduced. In the hyperprolactinaemic subjects, metyrosine had no effect on basal PRL nor on the virtually non-existent PRL response to DOM, whereas it abolished the exaggerated TSH response. The conclusion is drawn that the response of both PRL and TSH to DA receptor blockers is really dependent upon DA inhibitory tone. A fall in this tone can also be postulated as responsible for the hyporesponsiveness of PRL to DOM frequently observed in pathological hyperprolactinaemia. In addition, the fact that metyrosine also abolished the exaggerated TSH response to DOM shows that the latter is totally dependent on enhanced DA inhibition of the thyrotrophs. Lastly, the reduced PRL response to TRH after metyrosine indicates that DA partly determines the ability of the lactotrophs to respond to TRH.