CD56(bright) lymphocytes become abundant in the human uterus during every menstrual cycle, following the surge in pituitary-derived luteinizing hormone (LH), which initiates final oocyte maturation. While the uterus is host to some CD56(bright) cells prior to ovulation, the rapid increase is thought to be due to proliferation of the resident population, accompanied by recruitment of CD56(bright) lymphocytes from the circulation. The rapid increase in CD56(bright) cells is concurrent with the onset of decidualization, the transformation of uterine stromal cells into secretory decidual cells. Uterine CD56(bright) cells proliferate and differentiate to become the predominant lymphocytes of the post-ovulatory uterus. These distinct, tissue-specific natural killer (NK) cells either die prior to menses or increase in number during early pregnancy, and then decline toward the end of the first trimester. Since lymphocytes home to tissues from the circulation, we investigated mechanisms of NK cell traffic over the course of natural menstrual cycles by measuring functional interactions between CD56+ cells from blood and endothelial cells using the Stamper-Woodruff assay of lymphocyte adhesion to frozen tissue sections. While a baseline level of adhesion was maintained throughout the cycle, elevated l-selectin-dependent adhesion of peripheral blood CD56(bright) cells occurred during a peri-ovulatory window. However, there were no significant menstrual cycle-induced changes in the transcription of l-selectin, alpha 4 integrin or LFA-1, or in expression of these proteins by NK cells, suggesting that the enhanced adhesion was due to post-translational modifications of these molecules. Quantitative RT-PCR failed to amplify the message for LH receptor or the alpha or beta forms of progesterone or estrogen receptors from blood NK cell subsets. Thus, we conclude that the actions of LH, E(2,) and P(4) on NK cells that promote interactions with endothelium and potential uterine homing are indirectly mediated through the responsiveness of other cell types.