The combination of 2-methoxyestradiol (2ME) plus TRAIL produced similar cytotoxicity to that observed with current chemotherapeutic reagents. Cell cytotoxicity was measured by the MTS assay in a human normal ovarian surface epithelium cell line (HOSE) and in the UCI 101 ovarian cancer cell line. Cells were treated with ethanol vehicle (C), TRAIL 200 ng/mL for 18 hours, 2ME and the chemotherapeutics doxorubicin (DOX, 5 μM), paclitaxel (PTX, 5 μM), and cisplatin (CIS, 5 μM), were administered for 48 hours. Furthermore, 2ME for 48 hours with TRAIL or chemotherapeutic addition occurring 18 hours before the end of the experiment were tested. Using the Mann-Whitney test, statistical significance in change in cell cytotoxicity in respect to vehicle treated control (★) and in respect to individual administration (#) for each drug was set at P < .05.