TRANSIENT forebrain ischemia causes selective neuronal death in the hippocampal CA1 neurons. A short sublethal ischemic episode preceding ischemia of longer duration is known to increase tolerance against cell death. The mechanisms of this ischemic tolerance are still poorly understood. Here we show, using Ca2+imaging, that intracellular calcium ([Ca2+]i) elevation in CA1 neurons after an anoxic-aglycemic episode is markedly inhibited in the ischemia-tolerant gerbil. The hippocampus of gerbils which did not acquire tolerance showed a high [Ca2+]ielevation during the anoxicaglycemic episode, similar to controls. Since hypoxia/ischemia-induced neurodegeneration can be triggered by cytoplasmic Ca2+overload, the tolerant gerbil may regulate calcium and keep [Ca2+]ibelow the critical level for initiating neuronal death.NeuroReport9: 1875–1878 © 1998 Rapid Science Ltd.