The role of intermolecular disulfide linkages in transthyretin (TTR) amyloid fibril formation was investigated by comparing wild type TTR to Cys-10-Ala TTR which is incapable of disulfide formation. The Cys-10-Ala variant exhibits quaternary structural stability equal to the wild type protein under acidic denaturing conditions. Both Cys-10-Ala and wild type TTR were converted into amyloid fibrils by partial acid denaturation. There was no evidence of intermolecular disulfide formation in the case of wild type amyloid fibrils. These results are inconsistent with a recently proposed model stressing the importance of intermolecular disulfide linkages in TTR amyloid fibril formation, but are consistent with a model relying on noncovalent quaternary contacts made possible through an acid-mediated conformational change.