The aims of this study were to examine the role of oestrogen in a series of ER-positive ovarian cancer cell line models, including the first characterised lines with moderate-high levels of ER. The effects of oestrogen on growth were initially determined in nine ovarian cell lines possessing a range of ER from 0 to 132 fmol/mg protein. Sensitivity to oestrogen correlated with the level of ER expression in that concentrations of 17 β-oestradiol (E₂) between 10^-12 and 10^-6M stimulated the growth of the PEO1, PEO4, and PEO6 cell lines which possess moderate-high levels of receptors between 96 and 132 fmol/mg protein, whereas there was no change in the growth of the PEA1 and PEA2 cell lines which have an ER content of less than 30 fmol/mg protein. The growth of the ER negative lines PEO14, PEO16 and PE023 was also unchanged by E₂ treatment. Concentrations of E₂ which were stimulatory to the PEO1 cell line were inhibitory to a cisplatin-resistant derivative, PEO1^CDDP despite this also possessing moderate-high levels of ER. Effects of E₂ on growth were also examined in two ovarian xenograft models grown in nude mice; PEO4 and HOX60 which are ER-positive and ER-negative respectively. Exposure of the xenografts to a subcutaneously planted oestrogen pellet produced a significant inhibition in PEO4 growth but no difference in HOX60 growth as compared to controls. If these results reflect the clinical situation, then there is a valid case for the use of anti-oestrogen therapy in a subset of patients with ovarian tumours expressing moderate-high levels of ER. Agents which interfere with the TGF-α and IGF-mediated growth pathways may also have therapeutic benefit.