A comparative ultrastructural study of the organization of intermediate filaments (tonofilaments) within normal colonic epithelium and colonic carcinoma cells was carried out. The pattern of development of the specialized intermediate filament (IF) network, occurring during the differentiation of normal colonic epithelial cells, was examined to allow a more complete comparison with tumour cells of different degrees of differentiation. Essentially the IF system becomes more organized as the cells differentiate, resulting in the formation of a three-dimensional network loosely surrounding the nucleus, extending through the sub-terminal web and basal cytoplasm, and inserting into lateral desmosomes. Another system of IFs also runs directly between lateral desmosomes, lying parallel to the plasma-membrane and desmosomal plaque, without inserting directly into the junction. Alterations in the organization of the IF system were seen in tumour cells with the type and extent being dependent upon their location and degree of differentiation. Cells within areas of the tumour where some degree of glandular structure was retained exhibited major alterations in their microfilament-containing structures. However, their IF system was essentially intact and lateral desmosomes were still present in similar numbers to those seen in normal, partially differentiated mid-crypt cells. Apolar tumour cells within areas of the tumour where a gross loss of cryptal architecture had occurred exhibited a striking disorganization of their IF system. No parallel bundles of interdesmosomal tonofilaments were present beneath the cell surface and the majority of the three-dimensional network appeared to have collapsed around the nucleus, although some extensions to randomly distributed surface desmosomes still occurred. It appears that this disorganization of the IF system is associated with a loss of cell polarity and may involve alterations in putative IF-associated proteins important in the interaction of IFs with surface desmosomes or other cytoskeletal elements. A study of this phenomenon may shed light on both the means of IF organization and assembly and their role in normal cells as well as the possible role of alterations in cytoskeletal elements in the expression or maintenance of the malignant phenotype.