One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.