Several aspects of the intermediate filaments' molecular architecture remain mysterious despite decades Of Study. The growth process and the final architecture may depend on the physical, chemical, and biochemical environment. Aiming at clarifying this issue, we have revisited the structure of the human hair follicle by means of X-ray microdiffraction. We Conclude that the histology-based growth zones along the follicle are correlated to the fine architecture of the filaments deduced from X-ray microdiffraction. Our analysis reveals the existence of two major polymorph intermediate filament architectures. Just above the bulb, the filaments are characterized by a diameter of 100 angstrom and a low-density core. The following zone upwards is characterized by the lateral aggregation of the filaments into a compact network of filaments, by a contraction of their diameter (to 75 angstrom) and by the setting Lip of a long-range longitudinal ordering. In the upper zone, the small structural change associated with the tissue hardening likely concerns the terminal domains. The architecture of the intermediate filament in the upper zones could be specific to hard alpha-keratin whilst the other architecture found in the lower zone could be representative for intermediate filaments in a different environment. (c) 2005 Elsevier Inc. All rights reserved.