Activated microglia, immune competent cells in the vertebrate central nervous system, release cytotoxic substances, including reactive oxygen species and nitric oxide. The steroid hormone, progesterone, has been shown to have anti - inflammatory properties. Interestingly, progesterone and its derivatives are synthesized in astrocytes. Therefore, we evaluated in the present study whether progesterone suppresses the release of nitric oxide from microglia, using the microglial cell line BV - 2 as a model. BV - 2 cells were activated with LPS and NO release was quantified using the Griess reagent. Cells were cultured for 24 hours in LPS (10 mg/ml) either in the presence or absence of progesterone. We found that progesterone decreased NO release in a concentration - dependent manner. 30 mM almost completely suppressed NO release. Since NO production is usually attributed to nitric oxide synthase (NOS) activity, we inhibited enzyme activity using the NOS inhibitor, L - NMMA. Furthermore, the NOS inhibitor L - NMMA (100 mM) reduced the release of NO following LPS stimulation. Thus, our experiments indicate that the local production of progesterone in astrocytes may modulate microglial activity.