Objective: Prolactin (PRL), a peptide hormone produced by the pituitary gland, is involved in the interaction between the neuroendocrine and immune system. Since dopamine receptor antagonists increase serum levels of PRL, both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing means of communication between the nervous and immune systems. This study evaluated the effects of PRL and the dopamine antagonist domperidone (DOMP) on macrophage activity of female rats. Methods: Oxidative burst and phagocytosis of peritoneal macrophages were evaluated by flow cytometry. Samples of peritoneal liquid from female rats were first incubated with PRL (10 and 100 n M) for different periods. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 n M). Results: In vitro incubation of macrophages with 10 n M DOMP decreased oxidative burst, after 30 min, whereas the PMA-induced burst was decreased by DOMP 10 n M after 2 and 4 h. Treatment with PRL (10 and 100 n M) for 30 min decreased oxidative burst and rate of phagocytosis (10 n M). After 2 h of incubation, 10 n M PRL decreased oxidative burst and phagocytosis intensity, but increased the rate of phagocytosis. On the other hand, after 4 h, PRL 10 and 100 n M increased oxidative burst and the rate of phagocytosis, but decreased intensity of phagocytosis. Conclusions: These observations suggest that macrophage functions are regulated by an endogenous dopaminergic tone. Our data also suggest that both PRL and dopamine exert their action by acting directly on the peritoneal macrophage.