Polypeptide sequences encoding the single exons of human tropoelastin were synthesized and their conformations were studied in different solvents and at different temperatures by CD and (1)H NMR. The results demonstrated the presence of labile conformations such as poly-proline II helix (PPII) and beta-turns whose stability is strongly dependent on the microenvironment. Stable, periodic structures, such as alpha-helices, are only present in the poly-alanine cross-linking domains. These findings give a strong experimental basis to the understanding of the molecular mechanism of elasticity of elastin. In particular, they strongly support the description of the native relaxed state of the protein in terms of trans-conformational equilibria between extended and folded structures as previously proposed [Debelle, L., and Tamburro, A. M. (1999) Int. J. Biochem. Cell. Biol. 31, 261-272].