Transthyretin is the major amyloid fibril protein in many forms of familial systemic amyloidosis where a missense mutation creates an amyloidogenic protein, and in senile systemic amyloidosis in which wild-type transthyretin aggregates into amyloid fibrils. The amyloid deposits may consist of full-length transthyretin but is very often, in senile systemic amyloidosis always, a mixture of full-length transthyretin and C-terminal transthyretin fragments. The amyloid fibril protein mixture can be purified by extraction of fibrils followed by sequential gel filtration after solubilization in a solution of guanidine hydrochloride. Since the C-terminal transthyretin fragments lack cysteine residues, a method to separate full-length transthyretin from fragments by covalent chromatography has been developed.