Several pieces of evidence suggest the existence of a relationship between neuroendocrine and immune systems. Prolactin (PRL) has been demonstrated to modulate some immune responses and its influence seems to be permissive or inhibitory depending on its concentration. Previous studies have reported a reduced natural killer (NK) cell function in patients with hyperprolactinemia. In 36 patients (34 females and 2 males, aged 14-46 years) with hyperprolactinemia (mean +/- SEM PRL 142.2 +/- 42.1 micrograms/l) of tumorous (19 patients) and functional (17 patients) origins, NK activity of peripheral blood lymphocytes (PBL) was studied. Patients had NK cell activity against the K562 cell line which did not differ from that of lymphocytes from 36 age- and sex-matched healthy donors (mean +/- SEM lytic units (LU) 619.0 +/- 103.0 and 531.9 +/- 52.6 respectively). No correlation between PRL levels and LU values was found (r = 0.28). When patients with tumors or functional hyperprolactinemia were separately analysed no difference was found between these two groups (mean +/- SEM LU 690.0 +/- 117.7 vs. 606.0 +/- 148.8). In conclusion, our data demonstrate that neither the elevated PRL levels nor the PRL-secreting tumor per se interfere with the NK system of hyperprolactinemic patients.