Cell cultures are useful tools to study the mechanisms involved in cell death following hypoxia or ischemia. By manipulating the extracellular environment, conditions that closely mimic the conditions that are thought to occur in vivo can be produced. These conditions permit study of cell's reaction to the trauma under specific conditions. Monitoring of the extracellular pH and ionic environment in cell cultures is much easier than in vivo. Further, metabolites produced by injured cells can be quantitated easier from cultures than from tissues in vivo. Cell cultures have recently been used to examine in detail the neurotoxicity of glutamate. Intracellular Ca2+ increases appear to be involved in the mechanisms of neurotoxic cell death. This Ca2+ entry appears to be through the NMDA receptor's Ca2+ channel. Ischemic and hypoxic injury produced by mechanisms other than glutamate neurotoxicity appear to involve increases in intracellular Ca2+ by releasing internal Ca2+ stores or by the influx of extracellular Ca2+. This Ca2+ entry may be through voltage-gated channels of the NMDA channel, or may be attributable to membrane perturbations. Through the use of cell cultures, each of the mechanism's involvement in the injury can be delineated.