To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.