The ganglioside monoclonal antibody A2B5 has previously been used at the light microscopic level to label Alzheimer neurofibrillary tangles (NFTs). Light microscopic analysis, however, could not reveal whether the A2B5 antibody-labeled NFTs or membrane fragments associated with NFTs. Therefore, we used pre-embedding immunohistochemical electron microscopy to examine A2B5 labeling of NFT. We found that the A2B5 antibody does indeed label a NFT antigen associated with the paired helical filament (PHF) structure, while no significant labeling of membranes or membrane fragments was observed. However, no clear periodicity of the immunogold label on the PHF was found.