Prolactin markedly influences cellular and humoral immunity in animals, but there is little information on its role in men. The aim of this work was to study the immune effects of pharmacological modification of prolactin levels in 5 healthy individuals. Peripheral blood mononuclear cell proliferative response to mitogens and antigens, interleukin-2 (IL-2) production, soluble and membrane IL-2 receptor expression in peripheral blood mononuclear cells and serum soluble IL-2 receptors were successively measured during normoprolactinemia, during bromocriptine induced hypoprolactinemia and during metoclopramide induced hyperprolactinemia. There was a significant increase in cellular proliferation during hypoprolactinemia when compared with hyperprolactinemia. No concomitant changes in soluble or membrane receptor expression or IL-2 production were observed. It is concluded that lymphocyte proliferative response to mitogens is dependent on prolactin levels in man and that this effects is not mediated by IL-2 or its receptors. These results may be potentially relevant in clinic since changes in serum prolactin have been described in different autoimmune diseases.