As waves of apoptosis occur at postnatal day (P) 2, 9 and 15 in the retina we examined whether erythropoietin (Epo) mediated neuroprotection during physiological cell death periods may contribute to proper retinal development. Complete retinas were explanted and homogenised for RNA-extraction and subsequent RT-PCR-analysis or cultured as organotypic explants in DME- Medium for simultaneous factor treatment. We detected a significant increase in Epo-mRNA expression in the retina, liver and kidney during early development, coinciding with the aneamia of the newborn. The continous Eporeceptor (EpoR)- mRNA expression suggested neuroprotective activity of Epo in developing retinal neurons. Treatment of retinal whole-mount cultures with recombinant Epo resulted in a significant decrease of apoptotic cells at P2 and P15. Moreover, transforming growth factor beta (TGF-ß)-induced apoptosis was completely blocked by Epo when both factors were applied simultaneously. Investigations on the signaling pathway revealed that Epo leads to a significant decrease in Bax-mRNA whereas bcl-2 remained unchanged. In conclusion we propose that a balance between pro- apoptotic TGF-ß and anti-apoptotic Epo is important for proper retinal development.