Amyloid fibril formation and deposition are the basis for a wide range of diseases, including spongiform encephalopathies, Alzheimer's and Familial Amyloidotic Polyneuropathies (FAP). In certain forms of FAP, the amyloid fibrils are mostly constituted by variants of transthyretin (TTR), a homo-tetrameric protein with a total molecular weight of 55 kDa and 127 aminoacid residues per subunit, found in the cerebrospinal fluid and in the plasma. Until recently a lot of emphasis has been placed on the role of a low pH environment, for example found in the lysosomes, being required to dissociate the native tetrameric TTR and induce the formation of a monomeric amyloidogenic intermediate (Kelly (1998) Curr Opin Struct Biol 8, 101). We have reported on the isolation of TTR monomeric species at pH 7.0, near physiological ionic strengths and commonly encountered physiological protein concentrations (Quintas et al.I, (1997) FEBS Lett 418, 297). Based on several biophysical studies, we have also shown that this monomeric species is non-native and we proposed a model for amyloidogenesis, at commonly observed physiological conditions (Quintas et al., (1999) J. Biol. Chem in press). Here, we additionally report on the correlation between protein stability to chemical unfolding and the amyloidogenic potential of several TTR variants.