Programmed death is a ubiquitous feature of the development of the vertebrate nervous system. This death is prevented in vivo by trophic factors and by afferent input. Death of neurons can also be prevented in culture models of programmed death by trophic factors and by chronic depolarization with elevated concentrations of K+ in the culture medium. The latter effect is mediated by Ca2+ influx through voltage-gated channels and may prevent death by mimicking survival-promoting effects of naturally occurring electrical activity. Little is currently known about the mechanism by which either trophic factors or increased cytoplasmic Ca2+ promote survival.