The relationship between neuroendocrine regulation and the immune system has recently become the subject of intense investigations. The pituitary secretes both immunostimulatory (growth hormone and prolactin) and immunosuppressive (ACTH) hormones, and is thus involved in the control of immune functions. The present work was aimed at the study of the immunoregulatory properties of prolactin in selected in vitro and in vivo model situations. Prolactin was found to enhance recovery of the receptor for sheep red blood cells (in vitro). Compared with control cells, incubation with prolactin and/or prolactin containing sera significantly enhanced the capacity of trypsin treated lymphocytes from the peripheral blood of healthy volunteers to form E-rosettes. Chlorpromazine stimulated prolactin release in males, and lactation stimulated prolactin release in females raised the number of large granular lymphocytes in peripheral circulation. Sera containing elevated prolactin levels stimulated the metabolic activity of peripheral neutrophilic leukocytes. These results suggest that prolactin may stimulate selective functions of cellular immunity, and that it is involved in interactions between the nervous, the hormonal and the immune systems.