Abstract: The enhancing effects of morphine on monosodium glutamate (MSG) neurtotoxicity and its blocking by naloxone were studied through morphological observation,together with detectionof concentrations of intracellular free Ca²⁺(Ca²⁺i) by Ca²⁺ indicator Fura-2/AM and lactatedehydrogenase (LDH)efflux in the bathing medium in primary cultures from 14～17 d old mouse fetalcortex, it was found that 10 min pre-incubation of young cortical neurons(7 day in,vitro )withmorphine 10-7 or 10-6mol·L^-1 substantially increased LDH release from 105.7%±19.0%(treatedwith MSG alone)to l94.5%±17.7%and 214.0%±9.5%respectively after exposure to MSG0.1mmol·L^-1, but pre-incubation with morphine(10-7 or10-6 mol·L^-1)plus naloxone (0.1mmol·L-1) reversed the LDH release after treatment with the same concentration of MSG. Morphine(10-7 or 1O-6 mol·L^-1) produced little elevation ofCa²⁺i. However, when combined with MSG(0.1 mmol·L^-1) morphine elevated theCa²⁺i level much more than MSG alone, These resultssuggest that morphine markedly enhances excitotoxic neuron damage, which can be reversed bynaloxone. Overloading of intracellular Ca²⁺ may be a simultaneous pathological mechanismunderlying the neuronal damage and death that occur in excitatory toxicity.