Several cytokines play a crucial role in the defense of the host against protozoa belonging to the genus Leishmania. However, the role of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) in human leishmaniasis is still controversial. The aim of this work was to study, in an "in vitro" model, the interactions of human phagocytes with L. major. The U937 human monocytic cell line, differentiated with phorbol myristate acetate (PMA) or a combination of 1 alpha,25 dihydroxyvitamin D3 (VD) and retinoic acid (RA), was used in all the experiments. The rate of infection, as well as the production of TNF alpha and IL-6 by cells upon infection with promastigotes, were studied. It was found that, depending on the agent used for differentiation, U937 cells produced different patterns of cytokines. PMA differentiated cells produced significantly more TNF alpha, but less IL-6 than cells differentiated with VD-RA. No direct relationship was found between the ability of differentiated U937 cells to release TNF alpha or IL-6 and their leishmanicidal activity.