To identify proteins that play a role in the development of the mammalian visual cortex, we have used an immunosuppression and rapid immunization strategy to generate monoclonal antibodies to antigens that are present in area 17 of the cat during the peak of cortical plasticity but are downregulated near the end of the plastic period. We report here the immunohistochemical and immunobiochemical characterization of six monoclonal antibodies that identify antigens preferentially expressed in the cat visual cortex at 5 weeks of age. Monoclonal antibodies Cat-305 and Cat-306 detect three immunoreactive elements that are not present at birth but are present at 5 weeks. The majority of immunoreactivity is associated with a population of cells in the white matter that are absent at 15 weeks of age. At both 5 and 15 weeks, a very small number of neurons show intense immunoreactivity throughout all processes, resembling that achieved with a Golgi stain. In addition, a diffuse band of immunoreactivity in layer IV is largely restricted to cortical areas 17 and 18. Cat-307 recognizes a 150 kDa soluble protein present in small cytoplasmic inclusions. These cytoplasmic "dot" are present in all layers, but are most prominent in layer V. Cat-307 immunoreactivity is present at birth and is completely downregulated by 15 weeks. Cat-104 and Cat-105 recognize a 200 kDa insoluble protein present at birth and at 5 weeks, but markedly downregulated by 15 weeks. At birth, the white matter, subplate, and layer I are most densely labeled, while at 5 weeks labeling is densest in layers II, III, and V. Cat-402 recognizes a number of high-molecular-weight antigens that are differentially expressed at 5 and 15 weeks of age. Stained non-neuronal cells that resemble protoplasmic astrocytes are present in all layers at both 5 and 15 weeks. At 5 weeks, but not at birth or 15 weeks, darkly immunoreactive radial processes are observed that run through the full depth of the cortex. We show here that immunoreactivity for several different monoclonal antibodies is detected selectively during the period of maximal developmental plasticity. The results demonstrate that the cat visual cortex at 5 weeks of age is molecularly distinct from the cortex at 15 weeks.