Single human skin fibroblasts and the skin keratinocyte cell line HaCaT show contact guidance and elongate along narrow (1-2 microm) scratches in glass substratum. During cell division these cells orientate their mitotic spindles along the long axis of the cell. Immunofluorescence staining of actin, tubulin, chromatin, and the nuclear NuMA protein complex demonstrated that cell elongation along scratches is accompanied by a corresponding rearrangement in the cytoskeleton. The results and literature suggest the following steps in the interplay between outside-in and inside-out signalling in the regulation of cell division orientation by extracellular factors. The interaction of cell surface with an anisotropy in the local environment causes changes in F-actin organization, cell elongation and alignment of stress fibres along the cell axis. This is accompanied by a corresponding reorientation of microtubules. Microtubules mediate between cell shape changes dependent upon cell interaction with substratum or other cells, the cortical actin and the position of centrosomes. Centrosomes determine the position and orientation of the mitotic spindle. The astral and central microtubules of the mitotic spindle control the localization of contraction-relaxation in the cell cortex and the position of the constriction ring and cell division plane.