Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.