Embryonic stem (ES) cells are a suitable system to study events occurring during development. In the present work we show that the apoptotic program was activated in ES cells, either by simple removal of the reducing agent 2-mercaptoethanol (2-ME), or by addition of all trans-retinoic (ATRA) to embryoid bodies. In these two conditions, there was an increase in reactive oxygen species and antioxidants such as catalase, superoxide dismutase or phenol prevented ATRA-induced cell death. Neuronal differentiation was observed when undifferentiated ES cells were treated with ATRA in the absence of serum and the presence of 2-ME.