Evidence accumulates suggesting that 9-O-acetylated gangliosides, recognized by a specific monoclonal antibody (Jones monoclonal antibody), are involved in neuronal migration and axonal growth. These molecules are expressed in rodent embryos during the period of axon extension of peripheral nerves and are absent in adulthood. We therefore aimed at verifying if these molecules are re-expressed in adult rats during peripheral nerve regeneration. In this work we studied the time course of ganglioside 9-O-acetyl GD3 expression during regeneration of the crushed sciatic nerve and correlated this expression with the time course of axonal regeneration as visualized by immunohistochemistry for neurofilament 200 in the nerve. We have found that the ganglioside 9-O-acetyl GD3 is re-expressed during the period of regeneration and this expression correlates spatio-temporally with the arrival of axons to the lesion site. Confocal analysis of double and triple labeling experiments allowed the localization of this ganglioside to Schwann cells encircling growing axons in the sciatic nerve. Explant cultures of peripheral nerves also revealed ganglioside expressing reactive Schwann cells migrating from the normal and previously crushed nerve. Ganglioside 9-O-acetyl GD3 is also upregulated in DRG neurons and motoneurons of the ventral horn of spinal cord showing that the reexpression of this molecule is not restricted to Schwann cells. These results suggest that ganglioside 9-O-acetyl GD3 may be involved in the regrowth of sciatic nerve axons after crush being upregulated in both neurons and glia.