Epidural spinal cord stimulation (SCS) has been used as an effective method for managing pain and spasticity for over two decades. However, the mechanisms of these beneficial effects are largely unknown. Since neurotransmitters are likely to be involved, we examined the relationship between SCS and local segmental amino acid release into the spinal cord extracellular space. Microdialysis was performed during continuous epidural SCS in animals subjected to ischemic spinal cord injury. Recovery of amino acid neurotransmitters from stimulated, injured animals was compared to that from a control group. Evoked potentials from the cortex and spinal cord were recorded to insure adequate stimulation and stable cord function. A significant increase in the concentrations of glycine and taurine was seen before, during, and after 90 minutes of continuous stimulation and was independent of the degree of injury. Levels of the other putative amino acid neurotransmitters were not significantly elevated. These results suggest that amelioration of pain or spasticity by epidural SCS may result from maintenance of post-injury elevation in baseline glycine and taurine levels.