Early electron microscope studies of developing wool and hair established that trichocyte (hard alpha-) keratin fibers have a composite structure in which filaments, subsequently shown to belong to the class of intermediate filaments (IF), were embedded in a matrix of sulfur-rich proteins. These studies also showed that the IF aggregate in a variety of ways to form what have been termed macrofibrils. Assembly into sheets appears to be an important initial factor in aggregation, and in the present contribution the structural principles governing sheet formation are formulated and specific models for the interaction between neighboring IF in a sheet are proposed, based on existing X-ray diffraction, electron microscope, and crosslinking data. All of the trichocyte keratins so far examined by electron microscopy exhibit similar filament/matrix textures and the mechanism of sheet formation proposed here is likely to have general applicability. (C) 2003 Elsevier Science (USA). All rights reserved.