The effect of the human trophoblast hormones chorionic gonadotropin (hCG) and placental lactogen (hPL) on the expression of cytokines in peripheral blood mononuclear cell cultures was followed under a variety of culture conditions, (a) phytohemagglutinin stimulated cells (PHA-MSC), (b) allogenic mixed cells (AMC) and (c) spontaneously proliferating cells (SPC). A dose dependent enhanced release of IL-6, IL-1 beta and TNF-alpha by hCG and hPL was observed under all culture conditions. However, an inhibitory effect on the IL-2 release was seen in PHA-MSC by hPL and in AMC by hPL and hCG. The role of the suppression of IL-2 production/release on cytotoxicity towards trophoblast is discussed. These results suggest a sensitive, dose dependent hormonal control of the modulation of the immune response during pregnancy and strengthen the concept of a distinct regulation of monocytes and lymphocyte subpopulation by trophoblast hormones.