Evidence is accumulating for a facilitative role for estrogen in ovarian cancer. Although response to antiestrogen therapy has been poor, there is a distinct subset of patients that respond. Strategies for treatment of ovarian cancer would be improved by identification of patients likely to respond to hormonal therapy. Cell culture models that are responsive or resistant to estrogen and antiestrogen may be of value in finding markers that predict responsiveness to hormonal therapy. Several model cell lines have been generated that express ER and proliferate in response to estrogen in vitro. Further studies are needed to better characterize the response of these ER positive cells lines to estrogen in vivo in mouse xenograft models. Expression of many of the same genes are regulated by estrogen in breast and in ovarian cancer cell lines. One exception may be the HER-2/neu oncogene product, which is down-regulated by estrogen in responsive breast carcinoma cells but not in two ovarian carcinoma cell lines. Initial analyses of several estrogen responsive and one resistant cell model suggests the potential value of progesterone receptor presence and low levels of HER-2/neu expression for predicting responsiveness to hormonal therapy. Additional cell models need to be investigated to determine the frequency with which these markers are associated with antiestrogen resistance.