The effects of interleukin (IL)-1 and granulocyte-macrophage colony stimulating factor (GM-CSF), which are present in the mouse placenta, on the secretion of mouse placental lactogen (mPL)-1 and mPL-II by placental cells were tested in vitro. IL-1 alpha and IL-1 beta, 2.5 nmol/l each, significantly inhibited mPL-II secretion by cells from days 9 and 12 of pregnancy, but did not affect mPL-II secretion by cells from day 7 of pregnancy or mPL-I secretion by cells from days 7, 9 or 12 of pregnancy. GM-CSF had no effect on mPL-I and mPL-II secretion by cells from days 7, 9 or 12 of pregnancy. The inhibitory effects of IL-1 alpha and IL-1 beta on mPL-II secretion were completely eliminated by the addition of antibodies to IL-1 alpha and IL-1 beta respectively. Western blot analysis for mPL-II indicated that IL-1 alpha significantly reduced the intensity of the mPL-II band. Steady-state levels of mPL-II mRNA, assessed by Northern blot analysis, were reduced by incubation of placental cells from day 12 of pregnancy with 2.5 nmol/l IL-1 alpha for 5 days. Co-incubation of 0.25 pmol/l IL-1 alpha, 25 pmol/l IL-6, and 25 pmol/l tumor necrosis factor-alpha, each of which did not significantly inhibit mPL-II secretion by itself, together inhibited mPL-II secretion. These results suggest that IL-1, but not GM-CSF, is a potent inhibitor of mPL-II secretion after mid-pregnancy, and that the combined action of cytokines can inhibit mPL-II secretion.