The Structure and Chemistry of Human Hair 28 in recent years notably by the construction of surface lattices to account for X-ray diffraction and other data.59, 63-65 In a most elegant recent paper Ishii et al.66 have used isothermal titration calorimetry to follow the thermodynamics of the addition in solution of a recombinant type I hair keratin intermediate filament (KIF) protein to a type II hair KIF protein. The thermal responses of these additions enabled them to analyze the protein supramolecular assembly processes in a stepwise manner to the formation of complete intermediate filaments. Interpretations of the assembly processes were based upon the A 11 , A 22 and A 12 modes of anti- parallel association of the coiled-coil dimers derived from the earlier cross-linking studies. Despite the enormous amount of effort this and the earlier cross-linking studies have entailed, the precise three- dimensional arrangement of the coiled-coil keratin dimers within the 70 Å-diameter keratin IF remains elusive. As if overwhelmed by the elegance of Steinert’s original cross- linking experiments most working in the field have chosen to ignore the possibility that the study of in vitro KIF assembly processes through the use of human recombinant hair keratins might not reflect the structure of the intermediate filaments in intact human hair. The cross-linking work initiated by Steinert has given rise to a model of hair KIFs in which the coiled-coil dimers are essentially in anti-parallel arrangement. On the other hand there is significant evidence, dare I say incontrovertible physical evidence, that the coiled-coil dimers in the KIFs of trichokeratins such as human hair have an all-parallel arrangement. Principal arguments for this opposing view have been put forward by Max Feughelman and collaborators.67-70 In considering the aforementioned parallel and anti-parallel alternatives it is necessary to point out that for stretches of proteins in α-helical conformation, the charge separation arising from the inter-turn hydrogen bonds results in a macrodipole moment of n x 3.5 Debye units where n is the number of amino acids in the helix.71 The coiled-coil α-keratin dimer, where the type I and type II protein helices are parallel and in register alignment, will