(PRL) secretion was investigated in 12 undialyzed patients with chronic renal failure (CRF), 30 hemodialyzed patients (HD), 19 renal transplant (RT) recipients and 17 controls. Basal PRL levels in CRF and HD patients were higher than in controls and RT subjects. Plasma PRL values were higher in CRF than in HD patients. In the HD group, plasma PRL concentrations were significantly higher in men with reduced sexual potency than in those in which it was normal. After TRH stimulation in CRF and HD the PRL response was considerably less and the time of peak delayed with respect to the controls. In RT subjects PRL did not return towards baseline after 120 min. After bromocriptine, plasma PRL suppression in CFR and HD patients was lower than in controls and RT subjects. These findings suggest that some factor which accumulates in uremia, is only partially removed by hemodialysis, and might be responsible for the hyperprolactinemia and might also interfere with the binding of TRH and bromocriptine to their respective pituitary receptors. Although a pituitary defect seems to be prevalent, a concomitant hypothalamic disorder cannot be excluded. Hyperprolactinemia seems to play a role in the sexual disturbances showed by some HD men. Whatever the alterations responsible for the impaired PRL regulation in uremia are, they are reversed by successful renal transplant.