We have sought to determine (1) if thalamic neurons upregulate the growth associated protein GAP-43 as a response to injury, or if a peripheral nerve graft is required to induce, enhance or sustain such a response, and (2) if thalamic neurons with different regenerative potentials also display different GAP-43 responses. Levels of GAP-43 protein (detected by LM and EM immunohistochemistry) and of GAP-43 mRNA (detected by in situ hybridization) were compared in the thalamus of adult rats between 1 d and 180 d after making a stab lesion or after implanting a peripheral nerve autograft. Stab injury is a sufficient stimulus to cause a transient upregulation in GAP-43 expression by neurons in the thalamus (both around the graft tip and in particular in the thalamic reticular nucleus) in the first week after injury but this response is both prolonged, and enhanced in the presence of a peripheral nerve graft. In addition, we demonstrate directly, by double labelling, that neurons of the thalamic reticular nucleus displaying high levels of the mRNA for GAP-43, have axons regenerating in the distal portion of the graft. These findings lend direct support to the hypothesis that upregulation of the GAP-43 gene is essential for prolonged regenerative axonal growth. We also demonstrate GAP-43 protein in graft Schwann cells and in brain astrocytes close to the site of graft implantation.