Silver staining profiles of argyrophilic grains (AGs) and of neurofibrillary tangles (NFTs) of diffuse neurofibrillary tangles with calcification (DNTC, collectively as DNTC-NFTs) were examined for their relation to tau- and ubiquitin-like immunoreactivity (IR). Pairs of mirror sections were triple-fluorolabeled with an anti-PHF tau (AT8) antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that identifies fibrillary structures such as NFTs of Alzheimer's disease (AD). One of the paired sections was subsequently stained with Gallyas method (GAL), and the other with Campbell-Switzer method (CS). Comparison of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either GAL or CS enabled the determination of five different profiles of each structure: AT8-IR, ubiquitin-like-IR, affinity to TR, argyrophilia with GAL or CS staining. AGs, mainly composed of four-repeat (4R) tau, were argyrophilic with GAL but not with CS, and their affinity to TR and ubiquitin-like-IR was not intense. This staining profile of AGs is identical with those of tau-positive structures in the cortex of progressive supranuclear palsy/corticobasal degeneration, both composed of 4R tau. This selective affinity of AGs to GAL is in sharp contrast with Pick bodies, composed of three-repeat (3R) tau, that are positive for CS but not for GAL, as we reported previously. This contrast is explainable if the argyrophilia with CS is related to deposits containing 3R tau, while that with GAL is linked to those containing 4R tau. Indeed, DNTC-NFTs, that contain both 3R and 4R tau, were argyrophilic with CS and GAL, and their affinity to TR and ubiquitin-like-IR were consistent, as we reported previously for NFTs of AD and of Down's syndrome, both similarly composed of 3R and 4R tau. Taken together, differences in molecular composition of tau protein in these deposits are linked to their argyrophilic properties dependent on the staining method in these sporadic tauopathies. Although explanations for these empirical differences are not yet available, awareness of this clear distinction is potentially of diagnostic and pathological significance.