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To understand the mechanism by which amyloid fibrils form, we have been making real-time observations of the growth of individual fibrils, using total internal fluorescence microscopy combined with an amyloid-specific fluorescence dye, thioflavin T (ThT). At neutral pH, irradiation at 442 nm with a laser beam to excite ThT inhibited the fibril growth of ␤ 2 -microglobulin (␤2-m), a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Examination with a 22-residue K3 fragment of ␤2-m showed that the inhibition of fibril growth and moreover the destruction of preformed fibrils were coupled with the excitation of ThT. Several pieces of evidence suggest that the excited ThT transfers energy to ground state molecular oxygen, producing active oxygen, which causes various types of chemical modifications. The results imply a novel strategy for preventing the deposition of amyloid fibrils and for destroying preformed amyloid deposits.Amyloid fibrils are associated with the pathogenesis of more than 20 serious diseases, including Alzheimer, Parkinson, and Huntington diseases, and dialysis-related amyloidosis (1, 2). Moreover, various proteins and peptides that are not related to diseases can also form amyloid-like fibrils, implying that the formation of fibrils is a generic property of proteins and peptides (1). In basic structure, amyloid fibrils are long and often twisted, a few nanometers in diameter, and predominantly composed of cross ␤-sheets (1, 3). Amyloid fibrils are formed spontaneously with a lag phase or seed-dependently without a lag time, indicating that they are formed by nucleation and extension. Further understanding of the structure, mechanism of formation, and roles in amyloidosis is one of the most important issues of protein science today.To study amyloid fibrils, we developed a unique technique for their direct observation in which total internal reflection fluorescence microscopy (TIRFM) 2 is combined with amyloidspecific thioflavin T (ThT) fluorescence (4 -8). This technique provides important information about the morphology, growth rate, and extension direction of fibrils in real time at the single fibril level. We have applied the technique to the fibrils of ␤ 2 -microglobulin (␤2-m) responsible for dialysis-related amyloidosis and amyloid ␤ associated with Alzheimer disease (4 -8).␤2-m is a major component of amyloid fibrils deposited in dialysis-related amyloidosis, a common and serious complication in patients receiving hemodialysis for more than 10 years (9 -11). ␤2-m, a typical immunoglobulin domain made of 99 amino acid residues and seven ␤-stands, is present as the nonpolymorphic light chain of the class I major histocompatibility complex (12). Renal failure disrupts the clearance of ␤2-m from the serum and, moreover, ␤2-m does not pass through the dialysis membrane, resulting in an increase in the concentration of ␤2-m in blood by up to 50-fold. Although an increase in the concentration of ␤2-m is the most important risk factor for fibrillation, how...