We analyzed changes in the expression of mRNAs for the axonal growth- promoting cell recognition molecules L1.1, L1.2, and neural cell adhesion molecule (NCAM) after a rostral (proximal) or caudal (distal) spinal cord transection in adult zebrafish. One class of cerebrospinal nuclei (represented by the nucleus of the medial longitudinal fascicle, the intermediate reticular formation, and the magnocellular octaval nucleus) showed a robust renegerative response after both types of lesions as determined by retrograde tracing and/or in situ hybridization for GAP-43. A second class (represented by nucleus ruber, the nucleus of the lateral lemniscus, and the tangential nucleus) showed a regenerative response only after proximal lesion. After distal lesion, upregulation of L1.1 and L1.2 mRNAs, but not NCAM mRNA expression, was observed in the first class of nuclei. The second class of nuclei did not show any changes in their mRNA expression after distal lesion. After proximal lesion, both classes of brain nuclei upregulated L1.1 mRNA expression (L1.2 and NCAM were not tested after proximal lesion). In the glial environment distal to the spinal lesion, labeling for L1.2 mRNA but not L1.1 or NCAM mRNAs was increased. These results, combined with findings in the lesioned retinotectal system of zebrafish (Bernhardt et al., 1996), indicate that the neural-intrinsic regulation of cell recognition molecules after axotomy depends on the cell type as well as on the proximity of the lesion to the neuronal soma. Glial reactions differ for different regions of the CNS.