We report the generation of a previously unknown class of water-soluble organic-inorganic hybrid nanoclusters composed of silver and thioflavin T with remarkable fluorescent properties. These hybrid nanoclusters display an extra bright fluorescence in aqueous solutions without any detectable photobleaching. Furthermore, the fluorescent nanoclusters can be generated in situ by sensitized photoreduction of Ag+. Organic-inorganic nanoclusters have remarkable advantages over the known classes of fluorescent probes for the development of ultrasensitive biological assays, cell imaging, or studies of single molecules. As an example of a practical biological application, imaging of amyloid fibrils produced from recombinant mammalian prion proteins and nonprion proteins using hybrid nanoclusters is presented.