Pre-eclampsia is a multi-system disorder of pregnancy and is a major cause of maternal and fetal morbidity and mortality. Its aetiology is unclear, although apoptosis is increased in the villous placenta and has a suggested pathogenic role [1]. Both the intrinsic and extrinsic apoptotic pathways have been identified in placental trophoblast. Possible activators of the intrinsic pathway are reactive oxygen metabolites, generated by oxidative stress, as a result of inappropriate placental perfusion. Epidermal growth factor (EGF) suppresses the extrinsic pathway to apoptosis in trophoblasts in vitro; although no investigations of oxidative stress-induced intrinsic apoptosis have been performed [2]. In pre-eclampsia, there is a known reduction in circulating levels of EGF. To assess whether apoptosis induced via the intrinsic pathway in vitro, by hydroxyl radicals from hydrogen peroxide (H₂O₂), can be inhibited by the addition of exogenous EGF. Placental villous explants were taken from 3 randomly selected areas of normal term human placentae (n=6) and cultured with increasing concentrations of H₂O₂ (0, 100, 1000μmol/l) and EGF (0, 10, 100ng/ml) for 6 or 48 hours. Tissue was also pre-incubated with EGF for 24 hours prior to the addition of H₂O₂. Human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) were measured in the resulting media, using an enzymatic and radioimmunoassay; assessing cytotrophoblast differentiation and tissue viability, respectively. TUNEL staining for DNA fragmentation, a late event in apoptosis, was performed on paraffinised tissue sections and expressed as an apoptotic index (TUNEL positive nuclei/total nuclei). Tissue was also fixed for electron microscopy. There were no significant effects of H₂0₂ and/or EGF on LDH liberation or hCG production after 6 and 48 hours culture. However, the apoptotic index was increased at the highest dose of H₂O₂ at both time points (p≤0.03, Friedman’s statistical test). This apoptotic effect was diminished by the addition of EGF at either concentration (p≤0.05). Pre-incubation with EGF significantly reduced apoptosis in the absence of H₂O₂ (p≤0.03). Electron microscopy confirmed a reduction in cytotrophoblast apoptosis in explants cultured with EGF. This is the first time EGF has been shown to antagonise the intrinsic pathway of apoptosis in placental villous trophoblasts; a potential primary pathogenic event in pre-eclampsia. This study proposes the replacement of EGF as a therapeutic intervention in pre-eclampsia.