OBJECTIVE The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, PATIENTS Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. MAIN OUTCOME MEASURE The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. RESULTS The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. CONCLUSION The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.