The integration of embryonic stem (ES) cells as well-differentiated neuronal cells into the retinas of adult mice was investigated. ES cells were transplanted in adult mouse retinas by intravitreal injections. Neuronal differentiation of the ES cells was investigated by morphological and immunohistochemical examinations on post-operative days 5 and 30. ES cell apoptosis was examined by in situ terminal dUTP-biotin nick end labeling of DNA fragments. Differentiated ES cells growing along the retinal surface developed fine neuronal cell processes around cell nuclei and generated neuronal networks into the retinal inner plexiform layer (IPL) 30 days after transplantation. The differentiated ES cells expressed retinal and neuronal markers. Many apoptotic cells were recognized in transplanted ES cells at day 5 but not at day 30 after transplantation. ES cells may be useful for neural tissue regeneration in the adult mammalian retina.