Recently we devised the methenamine-silver (M-S) staining method for detecting amyloid of senile plaques. Subsequently it was noticed that this procedure also readily stains neurofibrillary tangles (NFT) and neuropil threads. However, the sensitivity of the M-S method as an NFT stain has not been determined. In order to clarify this point, we performed a quantitative study on NFT, comparing the M-S method with conventional Bodian method, Gallyas-Braak method, and Bielschowsky-Hirano method on brain samples from three Alzheimer-type dementia patients and two non demented subjects. In addition, NFT staining by the M-S method was also compared with staining by anti-tau and anti-ubiquitin antibodies. Our results indicate that the M-S method was as sensitive for NFT as the Gallyas-Braak procedure. Further-more, the M-S method stained not only intraneuronal NFT, but also extracellular NFT, some of which could not be identified by conventional silver staining techniques and by immunostaining for tau and ubiquitin. We conclude that the M-S method is useful for the routine examination of senile plaques and NFT.