The neurotoxic effects of sodium glutamate (MSG, 2.5 g.kg-1 sc) and the enhancing effects of neurotropic Herpesvirus hominis (HVH, 0.2 ml/mouse ip) on MSG toxicity were studied through histomorphological observations, together with detection of the concentration of both mitochondrial protein bound Ca2+ and intracellular free Ca2+ ([Ca2+]i) by the Tb3+ fluorescent probe and Ca2+ indicator Fura-2/AM, respectively. It was found that in 10-d-old mice the neurons in arcuate hypothalamic nucleus degenerated severely after treatment with HVH+MSG, showing swollen edematous cytoplasm, dark pyknotic nuclei as well as a decrease in the amount of the neurons. The hypothalamic and spinal cord mitochondrial Tb3+ relative fluorescent intensity increased from 20 +/- 3 and 20 +/- 1 to 28 +/- 5 and 34 +/- 6, ie, the mitochondrial protein bound Ca2+ reduced significantly. MSG elevated the [Ca2+]i levels from 0.11 +/- 0.03 to 0.69 +/- 0.19 mumol.L-1 by not only stimulating the Ca2+ influx but also releasing the Ca2+ from intracellular stores. These findings suggested that MSG neurotoxicity was probably related to the overloading of neuroplasmic Ca2+, the destruction of neuronal abilities to deplete or sequester the intracellular Ca2+, as well as the irreversible neuronal injury and death.