Thirty-five patients seen at the Mayo Clinic from 1968 to 1977 who had carpal tunnel syndrome and local deposition of amyloid without evidence of systemic amyloidosis were identified. The unlabeled immunoperoxidase method was used with antisera against purified amyloid proteins of the AA, A kappa, A lambda, AF/ASC1 (prealbumin) (transthyretin), and AB (beta 2-microglobulin) types. In 33 of the 35 patients, amyloid stained with antisera to transthyretin; in the remaining 2 patients, the amyloid did not stain with any antisera. Nine of the 35 patients had a monoclonal protein in the serum, and 2 had a monoclonal light chain in the urine. Systemic amyloidosis or multiple myeloma did not develop in any of these 11 patients. During follow-up, systemic amyloidosis developed in only 2 of the 35 patients: 1 had senile systemic amyloidosis and 1 had tissue that was inadequate for immunohistochemical staining. Amyloid localized to the tenosynovium consists of transthyretin, and systemic amyloidosis rarely develops.