The present study demonstrates that following A and/or C fiber stimulation of the sciatic nerve, glutamate levels increase significantly in the hindpaw extracellular space. In hindpaw dialysate, electrical stimulation (5 min) of the sciatic nerve at 2x, 20x, 50x or 200x threshold current required to produce a muscle twitch resulted in peak glutamate increases of 120.8 +/- 9%, 134.3 +/- 5%, 153.9 +/- 10% and 150.5 +/- 5% of basal levels, respectively. Application of 1% capsaicin to the sciatic nerve (10 min) to selectively activate C fibers resulted in a peak glutamate increase of 130.8 +/- 8% of basal levels. Aspartate levels did not change significantly in either paradigm. These data indicate that low and high intensity stimulation can result in peripheral release of glutamate, providing a major source of ligand for the glutamate receptors localized on peripheral primary afferents.