Human natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemic female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemic patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemic patients, as compared to normal controls and bromocriptine-treated subjects, correlated well with the decreased NK activity. Finally,'in vitro'incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man.