Apart from its hematopoietic function, erythropoietin (Epo) mediates neuroprotective activity. To examine whether Epo plays a role in cell death decisions during neurogenesis, we made use of the developing mouse retina as an excellent CNS model system. The retina is easily accessible and less complex than other neuronal tissues. Complete retinas were explanted and homogenised for RNA-extraction or cultured as organotypic explants in DMEM for subsequent factor treatment. Epo and Epo receptor (EpoR) expression in the retina was determined by RT-PCR on postnatal days 0 (P0) to 20 (P20). We detected a continuous expression of Epo-mRNA during postnatal retinal development. EpoR expression peaked on P15, exactly within a physiological phase of retinal apoptosis. Treatment of P15 retinal whole-mount cultures with rhEpo resulted in a significant decrease of apoptosis. Moreover, transforming growth factor beta (TGF-ß)-induced apoptosis was completely blocked by Epo when both factors were applied simultaneously. These data indicate that Epo antagonises physiological neuronal cell death as well as TGF-ß mediated retinal apoptosis. In conclusion we propose a balance between pro-apoptotic TGF-ß and anti-apoptotic Epo in the developing mouse retina