It has been well shown that apoptosis occurs in mammalian embryos as early as the blastocyst stage, in order to regulate the importance of the inner cell mass. We have looked for apoptosis at the cleavage stage, in human embryos that could not be transferred because of a high degree of fragmentation (grade IV) or a blockage in embryo development. Most of these embryos had blastomeres with condensed or fragmented chromatin, evocating apoptosis. Two markers of programmed cell death, detecting either early (Annexin V) or late (TUNEL technique) apoptosis events, were positive in our study: 100% and 30% of embryos were marked by Annexin V and TUNEL, respectively. Therefore, it seems that apoptosis occurs very early in human embryos conceived in vitro; this could represent a response to suboptimal culture conditions.