Alz-50 is a monoclonal antibody directed against an antigen present in Alzheimer's disease. Unlike conventional pathological stains that reveal only neurons with neurofibrillary tangles (NFTs), Alz-50 recognizes neurons that contain NFTs and additional neurons that do not. Our investigation of the topographical distribution of both NFT-containing and non-NFT-containing neurons recognized by Alz-50 reveals that they are both found primarily in certain cytoarchitectural areas and lamina that have been established as consistent sites for NFT pathology. Some of the neurons recognized by Alz-50 appear histopathologically normal. We suggest that Alz-50 recognizes an antigen in neurons that both precedes and accompanies NFT formation. Thus, it may mark a point early in cellular pathology before irreversible cytoskeletal and degenerative changes occur.