We have recently identified nip-2 as a gene target for 17beta-oestradiol activity in the neuroblastoma SK-ER3 cells expressing the oestrogen receptor (ER) alpha. Here we show 17beta-oestradiol treatment of neuroblastoma and rat embryo neurones in culture blocks the increase in nip-2 mRNA induced by apoptotic stimuli and prevents cell death as indicated by cell counting, 3,(4,5-dimethylthiazol-2-yl)2,5-diphenil-tetrazoliumbromi de and DNA fragmentation assays. Neither of these effects are observed in the presence of the specific ER antagonist ICI 182,780, and are absent in neuroblastoma cells not expressing ER. We propose that nip-2 plays a relevant role in neural cell apoptosis and that a decrease in its expression is instrumental for the oestrogen anti-apoptotic effect described here. The experimental evidence presented supports the recent hypothesis of a protective role of oestrogens in neurodegenerative diseases such as Alzheimer's disease and highlights the importance of the development of new ER ligands for the prevention of neural cell damage.