The hypothesis that release of adenosine following spinal cord injury (SCI) may provide neuroprotective feedback is explored. Consistent with this hypothesis, substantial release of adenosine, estimated to reach 100 mu M in the extracellular space, was detected by microdialysis sampling immediately following contusion SCI. There is also considerable release of excitatory amino acids following SCI. The latter was not affected by administration of the general adenosine receptor antagonist theophylline and the A, antagonist 8-cyclopentyl-1,3-dipropylxanthine, implying that the adenosine released following SCI does not significantly influence the release of neurotoxic amino acids. Administration of the concentration of glutamate released upon SCI into the spinal cord caused only about 1% as much release of adenosine as did injury, evidence that elevated excitatory amino acids do not elicit an appreciable fraction of the release of adenosine that follows SCI. Results obtained suggest that release of endogenous adenosine is not neuroprotective by blocking release of excitatory amino acids following SCI. (C) 2000 Elsevier Science B.V. All rights reserved.