Beta-amyloid precursor protein (APP) is the source of beta-amyloid, which forms the cores of senile plaques in Alzheimer's Disease. However, the function of this precursor protein is currently unknown and an adult animal in which this protein varied substantially would be valuable. We used subcutaneous diethyldithiocarbamate to reversibly lesion the olfactory epithelium in adult rats and found that whole-bulb levels of APP-like immunoreactivity significantly decreased after the lesion, then increased reaching almost five-fold normal levels six weeks after treatment. Growth cone associated protein (GAP43) decreased when the nerve degenerated, then increased, replicating previous studies of olfactory nerve regeneration. Immunocytochemical techniques identified APP immunoreactive perikarya and fibers in and around glomeruli at three days to one week post-lesion and upregulation of APP-like immunoreactivity in mitral cells and dendrites at five weeks. Olfactory nerve regeneration appears to be a useful in vivo model system to understand the regulation of APP-like proteins.