BACKGROUND During healthy pregnancy, T helper (Th) 1-type and inflammatory-type responses are down-regulated, and Th2-type and proinflammatory-type responses predominate. In Plasmodium falciparum-infected females, these responses induce enhanced production of tumor necrosis factor- alpha and interferon- gamma. METHODS To assess the respective implication of monocytes and T cells in this placental immunomodulation, we cocultured cells from delivering females living in an area where malaria is endemic. Monocytes and T cells from both peripheral and intervillous blood were crossed in in vitro cultures, to compare the proliferative response to several antigens. Moreover, monocyte cell-surface molecules were quantified by flow cytometry. RESULTS Coculture results confirmed placental immunomodulation and suggested that the most affected cells are not the intervillous monocytes, which are as able to present the antigen as the peripheral monocytes, but the intervillous T cells. Monocyte staining showed significant increases in human leukocyte antigen D-related, CD54, CD80, and CD86 surface markers in intervillous blood, compared with peripheral blood, which suggests a relative activation of monocytes in the placenta. CONCLUSION A state of T cell deactivation and monocyte activation is present at delivery. The T cell deactivation in reaction to purified protein derivative could be explained by the presence of local T cell immunoregulatory factors.