Monoclonal antibody Cat-301 recognizes a surface antigen on subsets of neurons in many areas of the mammalian CNS, including Y-cells in the cat dorsal lateral geniculate nucleus (LGN) and spinal motor neurons in several species. We have shown previously that the Cat-301 antigen is expressed relatively late in postnatal development, with a time course that matches that of late developmental features of both LGN and spinal cord neurons. The developmental time course of the expression of the Cat-301 antigen in the LGN correlates with the period during which visual deprivation can alter LGN Y-cells. Neonatal visual deprivation (by monocular lid suture or dark rearing) suppresses Cat-301 expression on Y-cells, while deprivation in adult animals has no effect on antigen expression. These results suggested that the onset of Cat-301 immunoreactivity provides a positive molecular marker for the end of a critical period in cat visual system development. To determine if Cat- 301 might be a general marker for experience-dependent development in other areas of the CNS we have examined antigen expression on hamster spinal cord motor neurons. Here, we report that Cat-301 immunoreactivity develops on hamster motor neurons between postnatal days 7 and 14. Altering neuromuscular activity by sciatic nerve crush or thoracic hemicordotomy inhibits Cat-301 expression on motor neurons if performed before the onset of Cat-301 immunoreactivity. Other motor neuron antigens are unaffected by this procedure. In adult animals, nerve crush or cordotomy has no effect on Cat-301 immunoreactivity, demonstrating that Cat-301 expression is not simply dependent on ongoing neural activity. These observations suggest that motor neurons, like LGN neurons, require some pattern of neuronal activity during a critical period in development and, further, that the phenotypic changes in neurons consequent to early activity are reflected by the expression of specific molecules. The identification and characterization of such molecules may yield a description of the molecular mechanisms of experience-dependent development.