While the effects of excitatory amino acids have been well characterized in the central nervous system, relatively little is known about their possible modulation of elements responsible for hyperalgesia within peripheral tissue. The presented experiments demonstrate that the intraplantar (i.pl.) injection of l-glutamate (30 nmol) evokes a thermal hyperalgesic response in the paw withdrawal latencies of normal rats which is stereospecific. In addition, the i.pl. injection of either the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 (10 nmol) acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (100 nmol) into hindpaws inflamed with carrageenan significantly reduced the thermal hyperalgesic response in rats. Collectively, these results suggest that excitatory amino acids activate a peripheral target which facilitates a hyperalgesic behavioral response to thermal stimulation via a receptor mediated process.