We studied the effect of increasing and decreasing the deuterium level on the mitochondrial membrane potential (MMP), Ca homeostasis, and neuronal death in the rat cerebellar neurons in vitro. It was found that decreasing deuterium concentration to 100 and 50 ppm was accompanied by gradual depression of MMP and a decrease in the level of cytosolic Ca compared to the baseline values at deuterium concentration 150 ppm. Increasing deuterium concentration to 300 and 750 ppm was associated with an increase in MMP and Ca levels. A decrease in deuterium concentration to 100 ppm and its increase to 300 and 750 ppm reduced neuronal death after glucose deprivation. A decrease in deuterium concentration to 50 ppm produced no protective effect. Possible mechanisms for these effects are proposed.