Antibodies specific to the neural cell adhesion molecule (NCAM‐total), the 180 × 10³ My component of NCAM (NCAM‐180) and polysialic acid (PSA) were used in immunohistochemistry and Western blots to detect the spatiotemporal dynamics of these molecules in development and regeneration of the retinotectal system of Pleurodeles waltl. NCAM‐total and NCAM‐180 are continuously expressed in the retina, optic nerve, and tectum of the developing and adult salamander. This is also found for the 140 × 10³ My component of NCAM in Western blots of the retina. In the larval retina, PSA is present in the inner plexiform layer (IPL) and a few cells in all nuclear layers. At metamorphosis, PSA expression in the retina strongly increases in the layer of cone photoreceptor somata. Several cells in the inner nuclear layer and Muller cell processes also begin to express PSA. This pattern persists into adulthood. The optic nerve and the tectum are strongly PSA‐immunoreactive throughout development. In the adult optic nerve and optic fiber pathway in the brain, PSA expression is selectively downregulated. In the crush‐lesioned adult optic nerve, regenerating fibers are NCAM‐180‐positive but PSA‐negative. This demonstrates a molecular difference between growing nerve fibers of Pleurodeles in development and in regeneration. PSA regulation is closely correlated with metamorphosis, thus suggesting that PSA expression may be under hormonal control. Some aspects of PSA and NCAM isoform expression patterns in the retinotectal system of salamanders differ considerably from that of other vertebrates. The substained expression of NCAM isoforms in adult salamanders might be due to secondary simplification (paedomorphosis). © 1993 Wiley‐Liss, Inc.