Perfluorocarbons have unique and valuable physical properties not found in Nature. By incorporating fluorine into proteins, it might be possible to produce biological molecules with novel and useful properties.  Fluorocarbons are intrinsically more hydrophobic than hydrocarbons, and because partitioning of hydrophobic residues out of the aqueous phase is a major driving force in protein folding, are expected to be more stable.  Our research has focused on the perfluorinated amino acid L-5,5,5,5',5',5'-hexafluoroleucine (hFLeu), which we have incorporated into de novo designed peptides.  Here we present a detailed investigation into the effect on structure and stability of systematically repacking the hydrophobic core of a model protein with hFLeu.  The starting point was a 27-residue peptide, a4-H, that adopts an antiparallel 4-a-helix bundle structure, and in which the hydrophobic core comprise six layers of leucine residues introduced at the "a" and "d" positions of the canonical heptad repeat. A series of peptides were synthesized in which the central two (a₄-F₂), four (a₄-F₄), or all six layers (a₄-F₆) of the core were substituted hFLeu.  The free energy of unfolding increases by 0.3 (kcal/mol)/hFLeu on repacking the central two layers and by an additional 0.12 (kcal/mol)/hFLeu on repacking additional layers, so that a₄-F₆ is ~25% more stable than the nonfluorinated protein a₄-H. One-dimensional proton, two-dimensional ¹H-¹⁵N HSQC, and ¹⁹F NMR spectroscopies were used to examine the effect of fluorination on the conformational dynamics of the peptide.  Unexpectedly, increasing the degree of fluorination also appears to result in peptides that possess a more structured backbone and less fluid hydrophobic core.  The latter only occurs in a₄-F₄ and a₄-F₆, suggesting that crowding of the hFLeu residues may restrict the amplitude and/or time scales for rotation of the side chains.