Macrophages, derived from blood monocytes, have a central role in inflammation, One important function is their role in extracellular proteolysis. Inflammatory reactions in the gingival region have been shown to aggravate during puberty and pregnancy, The altered hormonal state might influence the plasminogen activating system of the macrophages and thereby pericellular proteolysis. The aim of this study was therefore to investigate the influence of estradiol and progesterone on the plasminogen activating system of macrophages. Human monocyte cultures were prepared from peripheral blood monocytes from both men and women, The effect of estradiol and progesterone was studied in LPS-activated as well as non-activated cells. Immunochemical analyses were performed for t-PA, u-PA, PAI-1 and PAI-2. The results showed that t-PA, u-PA and PAI-1 were found only in trace amounts with no influence of estradiol and progesterone, The total production of PAI-2, intra-cellular and released, was reduced by estradiol and progesterone in combination. Monocytes from men and women showed no difference in this response, However, monocytes from women had a lower mean basal production of PAI-2, and also a lower increase in response to LPS than monocytes from men. The observed decrease in production of PAI-2 from monocytes in response to estradiol and progesterone may allow increased pericellular proteolysis which might contribute to an aggravation of gingivitis during periods of altered hormonal influence.