Gonadotropins have been implicated in the development of epithelial ovarian cancers. These tumors are derived from ovarian surface epithelium (OSE). The purpose of this study was to determine the effects of these hormones on DNA synthesis and spontaneous cell death in primary cultures of OSE and three immortalized OSE cultures. Primary cultures of OSE cells were generated from the ovaries of women with benign disease. The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on DNA synthesis and cell death were determined using [(3)H]thymidine incorporation and JAM assays. Significant inductions of DNA synthesis were demonstrated with LH in 4/12 (33%) primary cultures of OSE and 2/3 OSE cell lines and with FSH in 4/11 (36%) primary cultures of OSE and 2/3 OSE cell lines. A significant protection from cell death was also observed in the presence of FSH in 2/4 primary cultures of OSE and 1/3 OSE cell lines and in the presence of LH in 1/4 primary cultures of OSE and 2/3 OSE cell lines. The results indicate that while gonadotropins have the potential to induce cell proliferation and protect from cell death in OSE cells in vitro, their effects are variable in OSE cells from different women.