Within wool and hair follicle cells, differences in the. mode of assembly of intermediate filaments (IFs) into macrofibrils are key factors leading to the classification of different cortical cells as ortho, meso, or para cells. This paper offers a model for macrofibril formation based on the generic propensity of particles of high axial ratio to separate into isotropic and anisotropic phases above a certain low concentration. The statistical mechanical theories of Flory describing such behaviour in mesogenic polymers are applied to this case. The effects of random coil protuberances on the IF rods are deduced to be important in achieving the observed packing density in the mesophase. Observational evidence to support the mesophase hypothesis in the early stages of cell development is reviewed, providing considerable support for the model. (c) 2005 Elsevier B.V. All rights reserved.