Although the survival of neuronal cells is highly dependent on neural connections with afferents or targets,(10,14,15) little is known about the survival of immature neurons that have not yet encountered the partners. Herein, using cultures of isolated hippocampal neurons of rat embryos, we have attempted to elucidate the contribution of neurite outgrowth to neuron survival and found that neurons died at a certain degree of neurite length with apoptotic characteristics in cases of no contact with other neurons. The threshold was 143.4microm, which was about five times as long as the cell body diameter. It was altered by depolarization or in the presence of basic fibroblast growth factor. Thus, neurons may be designed to kill themselves if they cannot find their targets after exploration within a particular area, the extent of which is variable due to cellular conditions.