Objective: To clarify whether female sex steroids directly affect the bioactivity of the human endometrial CD16(neg) CD56(bright) natural killer (NK) cells. Design: In vitro study. Setting: University obstetrics and gynecology department. Patient(s): Thirteen women with histologically normal endometrium who were undergoing hysterectomy and seven women during the first trimester of pregnancy who were undergoing selective termination. Intervention(s): Endometrium or decidua was obtained. Main Outcome Measure(s): The effects of 17beta-estradiol or progesterone (10(-6), 10(-7), and 10(-8) M) on the proliferation, cytolytic activity, and cytokine secretion of the isolated endometrial CD16(neg) CD56(bright) NK cells were examined using a H-3-thymidine incorporation assay, Cr-51-releasing assay, and enzyme-linked immunosorbent assay, respectively. Result(s): Neither 17beta-estradiol nor progesterone had significant effects on the proliferation, cytolytic activity, and cytokine secretion of endometrial CD16(neg) CD56(bright) NK cells. Conclusion(s): Female sex steroids do not directly affect the bioactivity of the human endometrial CD 16(neg) CD56(bright) NK cells. (Fertil Steril((R)) 2003;79(Suppl):730-4. (C) 2003 by American Society for Reproductive Medicine.).