The neural cell adhesion molecule (NCAM) consists of three major isoforms with differing extents of intracellular domains. The largest, NCAM 180, may play an important role in the development and stabilization of cell contacts because of its interaction with the cytoskeleton, its accumulation at contact sites between cells, and age-dependent modifications of the immunoreactivity of its intracellular domain. The developmental expression pattern of NCAM 180 was examined in the cat visual cortex to explore its relation with the age-dependent decline of synaptic malleability. Western blot and immunohistochemical analyses were carried out by using a monoclonal antibody (D3) directed against an epitope of the intracellular domain specific to NCAM 180 and antibodies against all NCAM isoforms. The latter revealed a similar time course of increased expression during development by both Western blot and immunohistochemical analysis. In contrast, the D3 antibody showed an age-dependent increase of immunoreactivity by Western blot analysis and a decrease of reactivity by immunohistochemistry. In addition, the D3 antibody revealed characteristic developmental changes of immunoreactivity in the neuropil and distribution of immunopositive neuronal cell bodies in the different cortical laminae. The observations from this and another study (Kramer et al., 1997) suggest that the D3 antibody-specific NCAM 180 epitope is masked during the stabilization of connectivity.