During embryonic development, the extracellular matrix (ECM) promotes the production of differentiated products by epithelial cells and the migration of mesenchymal cells, and probably also plays a role in epithelial-mesenchymal transformation. Here we examine the role of the cell skeleton (actin, microtubules, intermediate filaments) in mediating matrix effects on mesenchymal cell morphology, migration, and formation. The interaction of both epithelial cells and mesenchymal cells with ECM seems to involve the actin cortex, which is best developed in the base of the epithelial cell, where it attaches to underlying matrix via membrane-intercalated receptors. To interact with the matrix, the fibroblast has appropriate ECM receptors and an actin cortex around the whole cell. The actin cortex is absolutely required for assumption of bipolar shape, elongation, and movement through the matrix. Since the cortex seems to be anchored to the matrix, it is unlikely that it moves during cell migration. A new hypothesis states that the microtubule- and intermediate filament-rich endoplasm, containing the nucleus, moves past the actin cortex-receptor-matrix complex into the newly synthesized front end of the mesenchymal cell to effect forward movement. When epithelial cells transform into mesenchyme in the embryo, or when they are induced to do this in vitro, they switch from the keratin intermediate filament profile to one rich in vimentin, and the effect of cell matrix interaction on cell shape is profoundly altered. Vimentin-actin interactions with ECM may be a major factor in the ability of a cell to become mesenchymal.(ABSTRACT TRUNCATED AT 250 WORDS)