Glutamate is an excitatory neurotransmitter in turtle and mammalian cortex. In high concentrations it is toxic to mammalian neurons and is an important mediator in the pathway that leads to neuronal death from anoxia. Turtle neurons are remarkably resistant to anoxic injury and we sought to determine whether part of this resistance could be attributed to the sensitivity of turtle neurons to glutamate toxicity. Embryonic turtle cortical neurons were grown for 25 days in dissociated cell culture using a modification of a method developed for murine cortical cell culture. Turtle neurons in dissociated culture were found to express glutamate receptors which include both N-methyl-D-aspartate (NMDA) and non-NMDA receptor types. Remarkably, these neurons survive 5 minute exposures to glutamate in concentrations up to 3 mM, doses 30 times the LD50 and 6 times the LD100 for mouse cortical neurons. Elucidating the mechanism for this resistance may suggest new strategies for brain protection.